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New Anticancer Agents Based on Natural Products
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New Anticancer Agents Based on Natural Products

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Chemical Biology".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 56331

Special Issue Editors

Dr. M. Mizerska-Kowalska

E-Mail Website
Guest Editor
Department of Virology and Immunology, Maria Curie-Sklodowska University, Akademicka 19, 20-033 Lublin, Poland
Interests: natural and synthetic anti-tumor and anti-viral compounds; tumor microenvironment; natural and synthetic pro-osteogenic compounds; neutral endopeptidase (NEP) as therapeutic target
Prof. Dr. Wojciech Płaziński

E-Mail Website
Guest Editor
1. Jerzy Haber Institute of Catalysis and Surface Chemistry Polish Academy of Sciences, Niezapominajek 8, 30-239 Krakow, Poland
2. Department of Biopharmacy, Faculty of Pharmacy, Medical University of Lublin, Chodźki 4A, 20-093 Lublin, Poland
Interests: molecular modelling and docking; anticancer agents; ADME analysis; in silico studies; small molecular drugs
Dr. Sylwia Sowa

E-Mail Website
Guest Editor
Department of Organic Chemistry, Maria Curie-Sklodowska University, Lublin, Poland
Interests: purification and chemical characterization of substances derived from natural sources; chemical modification and synthesis of natural substances
Prof. Dr. Roman Paduch

E-Mail Website
Guest Editor
Department of Virology and Immunology, Maria Curie-Sklodowska University, Lublin, Poland
Interests: biological and molecular studies; anticancer agents

Special Issue Information

Dear Colleagues,

According to the World Health Organization, cancers rank between the first and fourth leading causes of death worldwide. Unfortunately, these rates are becoming increasingly prominent in comparison to the rates of stroke and coronary heart disease in many countries. Prevention and treatment are the main strategies to control and restrict the incidence of cancers. Chemotherapy remains the main method of cancer treatment. Depending on their sources, drugs are considered as natural, semi-synthetic, or synthetic, including those used in cancer treatment. Natural products are especially convenient sources of potential drugs due to their complexity and biodiversity. Plants, microbes, marine organisms, etc. have been considered essential sources of this type of therapeutic. Natural products constitute a diverse group in terms of their origin, including unaltered products, their derivatives obtained via chemical modifications (semi-synthetic products), or defined mixtures of botanical drugs. Moreover, natural products are convenient pharmacophores to totally synthetic drugs. It is reported that 62 anticancer drugs based on natural products and 13 synthetic anticancer drugs based on natural pharmacophores were approved over the period 1981–2019. However, there is a continuing need for new anticancer drugs or agents supporting conventional cancer therapies due to the emergence of multidrug resistance and the overall toxicity of currently used drugs. This Special Issue is aimed at the presentation of newly discovered anticancer or adjuvant agents based on natural products focusing on the purification/synthesis and characterization thereof as well as biological studies on anticancer activities and potential mechanisms of action.

Dr. M. Mizerska-Kowalska
Prof. Dr. Wojciech Płaziński
Dr. Sylwia Sowa
Prof. Dr. Roman Paduch
Guest Editors

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Keywords

  • cancer treatment
  • natural products
  • cell cycle
  • apoptosis
  • metastasis
  • chemoprevention
  • cancer cells sensitization

Published Papers (24 papers)

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14 pages, 3291 KiB  
Article
Aloe-Emodin Overcomes Anti-Cancer Drug Resistance to Temozolomide and Prevents Colony Formation and Migration in Primary Human Glioblastoma Cell Lines NULU and ZAR
by Sabrina Staffieri, Veronica Russo, Maria Antonietta Oliva, Marika Alborghetti, Miriam Russo and Antonietta Arcella
Molecules 2023, 28(16), 6024; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules28166024 - 11 Aug 2023
Cited by 1 | Viewed by 1345
Abstract
Glioblastoma, the most dangerous and aggressive type of CNS tumor, appears resistant to many chemotherapy drugs. In the patient-derived glioma cell lines NULU and ZAR, which exhibit drug-resistant phenotypes, we investigated the effect of combined AE (Aloe-emodin) and TMZ (temozolomide) and found a [...] Read more.
Glioblastoma, the most dangerous and aggressive type of CNS tumor, appears resistant to many chemotherapy drugs. In the patient-derived glioma cell lines NULU and ZAR, which exhibit drug-resistant phenotypes, we investigated the effect of combined AE (Aloe-emodin) and TMZ (temozolomide) and found a significant additive inhibitory effect on cell growth and a promising cytotoxic effect on both cell lines compared to treatment with single agents. We also examined the effect of combined AE and TMZ treatment on the drug-resistance protein MGMT. The results suggest that using AE combined with traditional drugs restores drug resistance in both primary resistant cell lines (NULU and ZAR). Furthermore, migration assays and scratch tests showed that the combined use of AE and TMZ can slow down the colony formation and migration of glioblastoma cells. These convincing results suggest that AE could be a natural adjuvant agent to potentiate the effects of traditional drugs (TMZ) and overcome drug resistance in glioblastoma cells. Full article
(This article belongs to the Special Issue New Anticancer Agents Based on Natural Products)
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28 pages, 8908 KiB  
Article
Modes of Action of a Novel c-MYC Inhibiting 1,2,4-Oxadiazole Derivative in Leukemia and Breast Cancer Cells
by Min Zhou, Joelle C. Boulos, Ejlal A. Omer, Sabine M. Klauck and Thomas Efferth
Molecules 2023, 28(15), 5658; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules28155658 - 26 Jul 2023
Cited by 2 | Viewed by 1580
Abstract
The c-MYC oncogene regulates multiple cellular activities and is a potent driver of many highly aggressive human cancers, such as leukemia and triple-negative breast cancer. The oxadiazole class of compounds has gained increasing interest for its anticancer activities. The aim of this study [...] Read more.
The c-MYC oncogene regulates multiple cellular activities and is a potent driver of many highly aggressive human cancers, such as leukemia and triple-negative breast cancer. The oxadiazole class of compounds has gained increasing interest for its anticancer activities. The aim of this study was to investigate the molecular modes of action of a 1,2,4-oxadiazole derivative (ZINC15675948) as a c-MYC inhibitor. ZINC15675948 displayed profound cytotoxicity at the nanomolar range in CCRF-CEM leukemia and MDA-MB-231-pcDNA3 breast cancer cells. Multidrug-resistant sublines thereof (i.e., CEM/ADR5000 and MDA-MB-231-BCRP) were moderately cross-resistant to this compound (<10-fold). Molecular docking and microscale thermophoresis revealed a strong binding of ZINC15675948 to c-MYC by interacting close to the c-MYC/MAX interface. A c-MYC reporter assay demonstrated that ZINC15675948 inhibited c-MYC activity. Western blotting and qRT-PCR showed that c-MYC expression was downregulated by ZINC15675948. Applying microarray hybridization and signaling pathway analyses, ZINC15675948 affected signaling routes downstream of c-MYC in both leukemia and breast cancer cells as demonstrated by the induction of DNA damage using single cell gel electrophoresis (alkaline comet assay) and induction of apoptosis using flow cytometry. ZINC15675948 also caused G2/M phase and S phase arrest in CCRF-CEM cells and MDA-MB-231-pcDNA3 cells, respectively, accompanied by the downregulation of CDK1 and p-CDK2 expression using western blotting. Autophagy induction was observed in CCRF-CEM cells but not MDA-MB-231-pcDNA3 cells. Furthermore, microarray-based mRNA expression profiling indicated that ZINC15675948 may target c-MYC-regulated ubiquitination, since the novel ubiquitin ligase (ELL2) was upregulated in the absence of c-MYC expression. We propose that ZINC15675948 is a promising natural product-derived compound targeting c-MYC in c-MYC-driven cancers through DNA damage, cell cycle arrest, and apoptosis. Full article
(This article belongs to the Special Issue New Anticancer Agents Based on Natural Products)
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10 pages, 1123 KiB  
Communication
Phytochemical Analysis and In Vitro Antileukemic Activity of Alkaloid-Enriched Extracts from Vinca sardoa (Stearn) Pignatti
by Daniela De Vita, Claudio Frezza, Fabio Sciubba, Chiara Toniolo, Camilla Badiali, Rita Petrucci, Martina Bortolami, Paola Di Matteo, Daniele Rocco, Annarita Stringaro, Marisa Colone, Andrea Maxia, Maria Teresa Petrucci, Mauro Serafini and Sebastiano Foddai
Molecules 2023, 28(15), 5639; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules28155639 - 25 Jul 2023
Viewed by 929
Abstract
Vinca sardoa (Stearn) Pignatti, known as Sardinian periwinkle, is widely diffused in Sardinia (Italy). This species contains indole alkaloids, which are known to have a great variety of biological activities. This study investigated the antileukemic activity against a B lymphoblast cell line (SUP-B15) [...] Read more.
Vinca sardoa (Stearn) Pignatti, known as Sardinian periwinkle, is widely diffused in Sardinia (Italy). This species contains indole alkaloids, which are known to have a great variety of biological activities. This study investigated the antileukemic activity against a B lymphoblast cell line (SUP-B15) of V. sardoa alkaloid-rich extracts obtained from plants grown in Italy, in Iglesias (Sardinia) and Rome (Latium). All the extracts showed a good capacity to induce reductions in cell proliferation of up to 50% at the tested concentrations (1–15 µg/mL). Moreover, none of the extracts showed cytotoxicity on normal cells at all the studied concentrations. Full article
(This article belongs to the Special Issue New Anticancer Agents Based on Natural Products)
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14 pages, 1848 KiB  
Article
Phenolic Acids Rescue Iron-Induced Damage in Murine Pancreatic Cells and Tissues
by Tugba Kose, Paul A. Sharp and Gladys O. Latunde-Dada
Molecules 2023, 28(10), 4084; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules28104084 - 14 May 2023
Cited by 2 | Viewed by 1398
Abstract
Iron is an essential element involved in a variety of physiological functions. However, excess iron catalyzes the generation of reactive oxygen species (ROS) via the Fenton reaction. Oxidative stress, caused by an increase in intracellular ROS production, can be a contributory factor to [...] Read more.
Iron is an essential element involved in a variety of physiological functions. However, excess iron catalyzes the generation of reactive oxygen species (ROS) via the Fenton reaction. Oxidative stress, caused by an increase in intracellular ROS production, can be a contributory factor to metabolic syndromes such as dyslipidemia, hypertension, and type 2 diabetes (T2D). Accordingly, interest has grown recently in the role and use of natural antioxidants to prevent iron-induced oxidative damage. This study investigated the protective effect of the phenolic acids; ferulic acid (FA) and its metabolite ferulic acid 4-O-sulfate disodium salt (FAS) against excess iron-related oxidative stress in murine MIN6 cells and the pancreas of BALB/c mice. Rapid iron overload was induced with 50 μmol/L ferric ammonium citrate (FAC) and 20 μmol/L 8-hydroxyquinoline (8HQ) in MIN6 cells, while iron dextran (ID) was used to facilitate iron overload in mice. Cell viability was determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay, ROS levels were determined by dihydrodichlorofluorescein (H2DCF) cell-permeant probe, iron levels were measured by inductively coupled plasma mass spectrometry (ICP-MS), glutathione, SOD (superoxide dismutase) and lipid peroxidation, and mRNA were assayed with commercially available kits. The phenolic acids enhanced cell viability in iron-overloaded MIN6 cells in a dose-dependent manner. Furthermore, MIN6 cells exposed to iron showed elevated levels of ROS, glutathione (GSH) depletion and lipid peroxidation (p < 0.05) compared to cells that were protected by treatment with FA or FAS. The treatment of BALB/c mice with FA or FAS following exposure to ID increased the nuclear translocation of nuclear factor erythroid-2-related factor 2 (Nrf2) gene levels in the pancreas. Consequently, levels of its downstream antioxidant genes, HO-1, NQO1, GCLC and GPX4, increased in the pancreas. In conclusion, this study shows that FA and FAS protect pancreatic cells and liver tissue from iron-induced damage via the Nrf2 antioxidant activation mechanism. Full article
(This article belongs to the Special Issue New Anticancer Agents Based on Natural Products)
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14 pages, 5876 KiB  
Article
An Ethanol Extract of Perilla frutescens Leaves Suppresses Adrenergic Agonist-Induced Metastatic Ability of Cancer Cells by Inhibiting Src-Mediated EMT
by Jae-Hoon Jeong, Hyun-Ji Park, Gyoo-Yong Chi, Yung-Hyun Choi and Shin-Hyung Park
Molecules 2023, 28(8), 3414; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules28083414 - 12 Apr 2023
Cited by 2 | Viewed by 1388
Abstract
Previous studies have indicated that the adrenergic receptor signaling pathway plays a fundamental role in chronic stress-induced cancer metastasis. In this study, we investigated whether an ethanol extract of Perilla frutescens leaves (EPF) traditionally used to treat stress-related symptoms by moving Qi could [...] Read more.
Previous studies have indicated that the adrenergic receptor signaling pathway plays a fundamental role in chronic stress-induced cancer metastasis. In this study, we investigated whether an ethanol extract of Perilla frutescens leaves (EPF) traditionally used to treat stress-related symptoms by moving Qi could regulate the adrenergic agonist-induced metastatic ability of cancer cells. Our results show that adrenergic agonists including norepinephrine (NE), epinephrine (E), and isoproterenol (ISO) increased migration and invasion of MDA-MB-231 human breast cancer cells and Hep3B human hepatocellular carcinoma cells. However, such increases were completely abrogated by EPF treatment. E/NE induced downregulation of E-cadherin and upregulation of N-cadherin, Snail, and Slug. Such effects were clearly reversed by pretreatment with EPF, suggesting that the antimetastatic activity of EPF could be related to epithelial–mesenchymal transition (EMT) regulation. EPF suppressed E/NE-stimulated Src phosphorylation. Inhibition of Src kinase activity with dasatinib completely suppressed the E/NE-induced EMT process. Transfecting MDA-MB-231 cells with constitutively activated Src (SrcY527F) diminished the antimigration effect of EPF. Taken together, our results demonstrate that EPF can suppress the adrenergic agonist-promoted metastatic ability of cancer cells by inhibiting Src-mediated EMT. This study provides basic evidence supporting the probable use of EPF to prevent metastasis in cancer patients, especially those under chronic stress. Full article
(This article belongs to the Special Issue New Anticancer Agents Based on Natural Products)
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17 pages, 5486 KiB  
Article
Cellular Localization of Selected Porphyrins and Their Effect on the In Vitro Motility of Human Colon Tumors and Normal Cells
by Maciej P. Frant, Mariusz Trytek, Kamil Deryło, Mateusz Kutyła and Roman Paduch
Molecules 2023, 28(7), 2907; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules28072907 - 23 Mar 2023
Viewed by 1335
Abstract
Standard therapies for colorectal cancer cannot eliminate or sufficiently reduce the metastasis process. Photodynamic therapy (PDT) may be an alternative to minimizing this problem. Here, we examined the cellular localization of selected porphyrins and determined whether free-base and manganese (III) metallated porphyrins may [...] Read more.
Standard therapies for colorectal cancer cannot eliminate or sufficiently reduce the metastasis process. Photodynamic therapy (PDT) may be an alternative to minimizing this problem. Here, we examined the cellular localization of selected porphyrins and determined whether free-base and manganese (III) metallated porphyrins may limit colon cancer cells’ (HT29) or normal colon epithelial cells’ (CCD 841 CoTr) motility in vitro. White light irradiation was used to initiate the photodynamic effect. Porphyrin uptake by the cells was determined by porphyrin fluorescence measurements through the use of confocal microscopy. Free-base porphyrin was found in cells, where it initially localized at the edge of the cytoplasm and later in the perinuclear area. The concentrations of porphyrins had no effect on cancer cell migration but had a significant effect on normal cell motility. Due to the low concentrations of porphyrins used, no changes in F-actin filaments of the cellular cytoskeleton were detected. Signal transmission via connexons between neighbouring cells was limited to a maximum of 40 µm for HT29 and 30 µm for CCD 841 CoTr cells. The tested porphyrins differed in their activity against the tumor and normal cells’ migration capacity. Depending on the porphyrin used and the type of cells, their migration changed in relation to the control sample. The use of white light may change the activity of the porphyrins relative to the migratory capacity of the cells. The aim of the present study was to analyse the intracellular localization of tested porphyrins and their influence on the mobility of cells after irradiation with harmless white light. Full article
(This article belongs to the Special Issue New Anticancer Agents Based on Natural Products)
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18 pages, 3693 KiB  
Article
Chemical Evaluation of Liquidambar styraciflua L. Fruits Extracts and Their Potential as Anticancer Drugs
by Rafaela G. Pozzobon, Renata Rutckeviski, Juliane Carlotto, Vanessa S. Schneider, Lucimara M. C. Cordeiro, Graziele Francine Franco Mancarz, Lauro M. de Souza, Rosiane Guetter Mello and Fhernanda Ribeiro Smiderle
Molecules 2023, 28(1), 360; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules28010360 - 01 Jan 2023
Cited by 3 | Viewed by 1702
Abstract
Liquidambar styraciflua L. is an aromatic species, popularly used in traditional Chinese medicine to treat diarrhea, dysentery, coughs, and skin sores. The present study was designed to investigate the chemical composition and biological potential of extracts obtained from the fruits of this plant. [...] Read more.
Liquidambar styraciflua L. is an aromatic species, popularly used in traditional Chinese medicine to treat diarrhea, dysentery, coughs, and skin sores. The present study was designed to investigate the chemical composition and biological potential of extracts obtained from the fruits of this plant. For the chemical evaluation, it was used mainly liquid and gas chromatography, plus NMR, and colorimetric methods. The aqueous extract (EA) originated two other fractions: an aqueous (P-EA) and an ethanolic (S-EA). The three extracts were composed of proteins, phenolic compounds, and carbohydrates in different proportions. The analyses showed that the polysaccharide extract (P-EA) contained pectic polysaccharides, such as acetylated and methyl esterified homogalacturonans together with arabinogalactan, while the fraction S-EA presented phenolic acids and terpenes such as gallic acid, protocathecuic acid, liquidambaric acid, combretastatin, and atractyloside A. EA, P-EA, and S-EA showed antioxidant activity, with IC50 values of 4.64 µg/mL, 16.45 µg/mL, and 3.67 µg/mL, respectively. The cytotoxicity followed the sequence S-EA > EA > P-EA, demonstrating that the toxic compounds were separated from the non-toxic ones by ethanol precipitation. While the fraction S-EA is very toxic to any cell line, the fraction P-EA is a promising candidate for studies against cancer due to its high toxicity to tumoral cells and low toxicity to normal cells. Full article
(This article belongs to the Special Issue New Anticancer Agents Based on Natural Products)
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20 pages, 5104 KiB  
Article
The Lipophilic Purine Nucleoside—Tdp1 Inhibitor—Enhances DNA Damage Induced by Topotecan In Vitro and Potentiates the Antitumor Effect of Topotecan In Vivo
by Irina A. Chernyshova, Aleksandra L. Zakharenko, Nikolay N. Kurochkin, Nadezhda S. Dyrkheeva, Tatyana E. Kornienko, Nelly A. Popova, Valeriy P. Nikolin, Ekaterina S. Ilina, Timofey D. Zharkov, Maxim S. Kupryushkin, Vladimir E. Oslovsky, Mikhail S. Drenichev and Olga I. Lavrik
Molecules 2023, 28(1), 323; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules28010323 - 31 Dec 2022
Cited by 4 | Viewed by 1426
Abstract
The use of cancer chemotherapy sensitizers is a promising approach to induce the effect of clinically used anticancer treatments. One of the interesting targets is Tyrosyl-DNA Phosphodiesterase 1 (Tdp1), a DNA-repair enzyme, that may prevent the action of clinical Topoisomerase 1 (Top1) inhibitors, [...] Read more.
The use of cancer chemotherapy sensitizers is a promising approach to induce the effect of clinically used anticancer treatments. One of the interesting targets is Tyrosyl-DNA Phosphodiesterase 1 (Tdp1), a DNA-repair enzyme, that may prevent the action of clinical Topoisomerase 1 (Top1) inhibitors, such as topotecan (Tpc). Tdp1 eliminates covalent Top1-DNA (Top1c) complexes that appear under the action of topotecan and determines the cytotoxic effect of this drug. We hypothesize that Tdp1 inhibition would sensitize cells towards the effect of Tpc. Herein, we report the synthesis and study of lipophilic derivatives of purine nucleosides that efficiently suppress Tdp1 activity, with IC50 values in the 0.3–22.0 μM range. We also showed that this compound class can enhance DNA damage induced by topotecan in vitro by Comet assay on human cell lines HeLa and potentiate the antitumor effect of topotecan in vivo on a mice ascitic Krebs-2 carcinoma model. Thereby, this type of compound may be useful to develop drugs, that sensitize the effect of topotecan and reduce the required dose and, as a result, side effects. Full article
(This article belongs to the Special Issue New Anticancer Agents Based on Natural Products)
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16 pages, 2360 KiB  
Article
Alpha Ketoglutarate Downregulates the Neutral Endopeptidase and Enhances the Growth Inhibitory Activity of Thiorphan in Highly Aggressive Osteosarcoma Cells
by Magdalena Mizerska-Kowalska, Adrianna Sławińska-Brych, Emilia Niedziela, Viktor Brodovskiy and Barbara Zdzisińska
Molecules 2023, 28(1), 97; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules28010097 - 22 Dec 2022
Viewed by 1898
Abstract
Since natural substances are widely explored as epigenetic modulators of gene expression and epigenetic abnormalities are important causes of cancerogenesis, factors with pro-tumor activities subjected to epigenetic control, e.g., neutral endopeptidase (NEP, neprilysin), are promising anticancer targets for potential therapies acting via epigenetic [...] Read more.
Since natural substances are widely explored as epigenetic modulators of gene expression and epigenetic abnormalities are important causes of cancerogenesis, factors with pro-tumor activities subjected to epigenetic control, e.g., neutral endopeptidase (NEP, neprilysin), are promising anticancer targets for potential therapies acting via epigenetic regulation of gene expression. Alpha-ketoglutarate (AKG) is a naturally occurring co-substrate for enzymes involved in histone and DNA demethylation with suggested anti-cancer activity. Hence, we investigated a potential effect of AKG on the NEP expression in cells derived from various cancers (cervical, colon, osteosarcoma) and normal epithelial cells and osteoblasts. Moreover, the overall methylation status of histone H3 was explored to establish the molecular target of AKG activity. Additionally, it was investigated whether AKG in combination with thiorphan (NEP specific inhibitor) exhibited enhanced anticancer activity. The results revealed that AKG downregulated the expression of NEP at the protein level only in highly aggressive osteosarcoma HOS cells (flow cytometry and fluorometric assays), and this protease was found to be involved in AKG-induced growth inhibition in osteosarcoma cells (siRNA NEP silencing, BrdU assay, flow cytometry). Unexpectedly, AKG-induced hypermethylation of H3K27 in HOS cells, which was partially dependent on EZH2 activity. However, this effect was not implicated in the AKG-induced NEP downregulation (flow cytometry). Finally, the combined treatment with AKG and thiorphan was shown to significantly enhance the growth inhibitory potential of each one towards HOS cells (BrdU assay). These preliminary studies have shown for the first time that the downregulation of NEP expression is a promising target in therapies of NEP-implicating HOS cells. Moreover, this therapeutic goal can be achieved via AKG-induced downregulation of NEP and synergistic activity of AKG with thiorphan, i.e., a NEP specific inhibitor. Furthermore, this study has reported for the first time that exogenous AKG can influence the activity of histone methyltransferase, EZH2. However, this issue needs further investigation to elucidate the mechanisms of this phenomenon. Full article
(This article belongs to the Special Issue New Anticancer Agents Based on Natural Products)
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12 pages, 9252 KiB  
Article
Evaluation of In Vitro Cytotoxic Potential of Avarol towards Human Cancer Cell Lines and In Vivo Antitumor Activity in Solid Tumor Models
by Tatjana P. Stanojkovic, Marina Filimonova, Nadja Grozdanic, Slavica Petovic, Anna Shitova, Olga Soldatova, Alexander Filimonov, Jelena Vladic, Petr Shegay, Andrey Kaprin, Sergey Ivanov and Marina Nikitovic
Molecules 2022, 27(24), 9048; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27249048 - 19 Dec 2022
Cited by 2 | Viewed by 1621
Abstract
The goal of this study was to determine the activity in vitro and in vivo of avarol, a sesquiterpene hydroquinone originating from the Dysidea avara sponge from the south Adriatic Sea, against different cancer cell lines and two types of mouse carcinoma. To [...] Read more.
The goal of this study was to determine the activity in vitro and in vivo of avarol, a sesquiterpene hydroquinone originating from the Dysidea avara sponge from the south Adriatic Sea, against different cancer cell lines and two types of mouse carcinoma. To investigate the in vitro cytotoxicity, a human cervix adenocarcinoma cell line (HeLa), human colon adenocarcinoma (LS174), human non-small-cell lung carcinoma (A549), and a normal human fetal lung fibroblast cell line (MRC-5) were used. The in vivo antitumor activity was investigated against two transplantable mouse tumors, the Ehrlich carcinoma (EC) and cervical cancer (CC-5). The effect of avarol on cancer cell survival, which was determined by the microculture tetrazolium test, confirmed a significant in vitro potency of avarol against the investigated cell lines, without selectivity towards MRC-5. The highest cytotoxicity was exhibited against HeLa cancer cells (10.22 ± 0.28 μg/mL). Moreover, potent antitumor activity against two tumor models was determined, as the intraperitoneal administration of avarol at a dose of 50 mg/kg resulted in a significant inhibition of tumor growth in mice. After three administrations of avarol, a 29% inhibition of the EC growth was achieved, while in the case of CC-5, a 36% inhibition of the tumor growth was achieved after the second administration of avarol. Therefore, the results indicate that this marine sesquiterpenoid hydroquinone could be a promising bioactive compound in the development of new anticancer medicine. Full article
(This article belongs to the Special Issue New Anticancer Agents Based on Natural Products)
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25 pages, 9042 KiB  
Article
Targeting Proteolysis with Cyanogenic Glycoside Amygdalin Induces Apoptosis in Breast Cancer Cells
by Valentina Cecarini, Salima Selmi, Massimiliano Cuccioloni, Chunmei Gong, Laura Bonfili, Yadong Zheng, Manuela Cortese, Mauro Angeletti, Soumaya Kilani and Anna Maria Eleuteri
Molecules 2022, 27(21), 7591; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27217591 - 05 Nov 2022
Cited by 5 | Viewed by 1839
Abstract
Background: Breast cancer is the most diagnosed cancer among women, and its incidence and mortality are rapidly growing worldwide. In this regard, plant-derived natural compounds have been shown to be effective as chemotherapeutic and preventative agents. Apricot kernels are a rich source of [...] Read more.
Background: Breast cancer is the most diagnosed cancer among women, and its incidence and mortality are rapidly growing worldwide. In this regard, plant-derived natural compounds have been shown to be effective as chemotherapeutic and preventative agents. Apricot kernels are a rich source of nutrients including proteins, lipids, fibers, and phenolic compounds and contain the aromatic cyanogenic glycoside amygdalin that has been shown to exert a cytotoxic effect on cancer cells by affecting the cell cycle, inducing apoptosis, and regulating the immune function. Methods: Here, we describe a previously unexplored proapoptotic mechanism of action of amygdalin in breast cancer (MCF7) cells that involves the modulation of intracellular proteolysis. For comparative purposes, the same investigations were also conducted upon cell treatment with two apricot kernel aqueous extracts from Prunus armeniaca L. Results: We observed that both the 20S and 26S proteasome activities were downregulated in the MCF7 cells upon 24 h treatments. Simultaneously, the autophagy cascade resulted in being impaired due to cathepsin B and L inhibition that also contributed to a reduction in cancer cell migration. The inhibition of these proteolytic systems finally promoted the activation of apoptotic events in the MCF7 cells. Conclusion: Collectively, our data unveil a novel mechanism of the anticancer activity of amygdalin, prompting further investigations for potential application in cancer preventative strategies. Full article
(This article belongs to the Special Issue New Anticancer Agents Based on Natural Products)
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24 pages, 5686 KiB  
Article
Structure Activity Relationship Studies around DB18, a Potent and Selective Inhibitor of CLK Kinases
by Dabbugoddu Brahmaiah, Anagani Kanaka Durga Bhavani, Pasula Aparna, Nangunoori Sampath Kumar, Hélène Solhi, Rémy Le Guevel, Blandine Baratte, Thomas Robert, Sandrine Ruchaud, Stéphane Bach, Surender Singh Jadav, Chada Raji Reddy, Paul Mosset, Nicolas Gouault, Nicolas Levoin and René Grée
Molecules 2022, 27(19), 6149; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27196149 - 20 Sep 2022
Viewed by 1549
Abstract
Three series of our lead CLK1 inhibitor DB18 have been designed, synthetized and tested against CLKs and DYRK1A kinases. Their cytotoxicity was subsequently measured on seven representative cancer cell lines. Guided by docking experiments, we focused on the less constrained part of the [...] Read more.
Three series of our lead CLK1 inhibitor DB18 have been designed, synthetized and tested against CLKs and DYRK1A kinases. Their cytotoxicity was subsequently measured on seven representative cancer cell lines. Guided by docking experiments, we focused on the less constrained part of the scaffold, and showed that drastically different substituents can be tolerated here. This work ended with the discovery of another promising derivative 12g, with IC50 = 0.004 µM in the inhibition of HsCLK1 and IC50 = 3.94 µM for the inhibition of HsDYRK1A. The SAR results are discussed in the light of extensive molecular modeling analyses. Finally, a kinome scan (463 human kinases) confirmed the outstanding selectivity of our lead compound DB18, suggesting that this scaffold is of prominent interest for selective CLK inhibitors. Altogether, these results pave the way for the development of inhibitors with novel selectivities in this family of kinases. Full article
(This article belongs to the Special Issue New Anticancer Agents Based on Natural Products)
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18 pages, 5881 KiB  
Article
New Polymethoxyflavones from Hottonia palustris Evoke DNA Biosynthesis-Inhibitory Activity in An Oral Squamous Carcinoma (SCC-25) Cell Line
by Jakub W. Strawa, Katarzyna Jakimiuk, Łukasz Szoka, Krzysztof Brzezinski, Paweł Drozdzal, Jerzy A. Pałka and Michał Tomczyk
Molecules 2022, 27(14), 4415; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27144415 - 10 Jul 2022
Cited by 6 | Viewed by 1827
Abstract
Four new compounds, 5-hydroxy-2′,6′-dimethoxyflavone (4), 5-hydroxy-2′,3′,6′-trimethoxyflavone (5), 5-dihydroxy-6-methoxyflavone (6), and 5,6′-dihydroxy-2′,3′-dimethoxyflavone (7), and three known compounds, 1,3-diphenylpropane-1,3-dione (1), 5-hydroxyflavone (2), and 5-hydroxy-2′-methoxyflavone (3), were isolated from the aerial parts [...] Read more.
Four new compounds, 5-hydroxy-2′,6′-dimethoxyflavone (4), 5-hydroxy-2′,3′,6′-trimethoxyflavone (5), 5-dihydroxy-6-methoxyflavone (6), and 5,6′-dihydroxy-2′,3′-dimethoxyflavone (7), and three known compounds, 1,3-diphenylpropane-1,3-dione (1), 5-hydroxyflavone (2), and 5-hydroxy-2′-methoxyflavone (3), were isolated from the aerial parts of Hottonia palustris. Their chemical structures were determined through the use of spectral, spectroscopic and crystallographic methods. The quantitative analysis of the compounds (1–7) and the zapotin (ZAP) in methanol (HP1), petroleum (HP6), and two chloroform extracts (HP7 and HP8) were also determined using HPLC-PDA. The biological activity of these compounds and extracts on the oral squamous carcinoma cell (SCC-25) line was investigated by considering their cytotoxic effects using the MTT assay. Subsequently, the most active compounds and extracts were assessed for their effect on DNA biosynthesis. It was found that all tested samples during 48 h treatment of SCC-25 cells induced the DNA biosynthesis-inhibitory activity: compound 1 (IC50, 29.10 ± 1.45 µM), compound 7 (IC50, 40.60 ± 1.65 µM) and extracts ZAP (IC50, 20.33 ± 1.01 µM), HP6 (IC50, 14.90 ± 0.74 µg), HP7 (IC50, 16.70 ± 0.83 µg), and HP1 (IC50, 30.30 ± 1.15 µg). The data suggest that the novel polymethoxyflavones isolated from Hottonia palustris evoke potent DNA biosynthesis inhibitory activity that may be considered in further studies on experimental pharmacotherapy of oral squamous cell carcinoma. Full article
(This article belongs to the Special Issue New Anticancer Agents Based on Natural Products)
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22 pages, 6244 KiB  
Article
Proapoptotic Effect and Molecular Docking Analysis of Curcumin–Resveratrol Hybrids in Colorectal Cancer Chemoprevention
by Gustavo Moreno-Q, Angie Herrera-R, Andres F. Yepes, Tonny W. Naranjo and Wilson Cardona-G
Molecules 2022, 27(11), 3486; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27113486 - 28 May 2022
Cited by 7 | Viewed by 2097
Abstract
Different hybrids based on curcumin and resveratrol were previously synthesized and characterized by spectroscopic techniques. The most active molecules (3a, 3e, 3i, and 3k) were evaluated in vitro as an approach to determine the possible mechanism of action [...] Read more.
Different hybrids based on curcumin and resveratrol were previously synthesized and characterized by spectroscopic techniques. The most active molecules (3a, 3e, 3i, and 3k) were evaluated in vitro as an approach to determine the possible mechanism of action of the hybrids. The results indicated that the evaluated curcumin/resveratrol hybrids induce mitochondrial instability in SW620 and SW480 cells. Moreover, these molecules caused a loss in membrane integrity, suggesting an apoptotic process mediated by caspases after the treatment with compounds 3i (SW480) and 3k (SW620). In addition, the results suggest that the mechanism of action of the hybrids could be independent of the p53 status. Furthermore, hybrids 3e and 3i caused G0/G1 phase arrest, which highlights the potential of these molecules not only as cytotoxic but also as cytostatic compounds. Hybrids 3e and 3i caused a negative modulation of the matrix metalloproteinase 7 (MMP7) on SW480 cells. These curcumin resveratrol hybrids could be potential candidates for further investigations in the search for potential chemopreventive agents, even in those cases with resistance to conventional chemotherapy because of the lack of p53 expression or function. Molecular docking simulations showed that compounds 3e, 3i, and 3k bind efficiently to proapoptotic human caspases 3/7 proteins, as well as human MMP-7 and p53, which, in turn, could explain at the molecular level the in vitro cytotoxic effect of these compounds in SW480 and SW620 colon cancer cell lines. Full article
(This article belongs to the Special Issue New Anticancer Agents Based on Natural Products)
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15 pages, 4715 KiB  
Article
Synergistic Interactions between Tocol and Phenolic Extracts from Different Tree Nut Species against Human Cancer Cell Lines
by Jazmín C. Stevens-Barrón, Abraham Wall-Medrano, Emilio Álvarez-Parrilla, Imelda Olivas-Armendáriz, Humberto Astiazaran-García, Ramón E. Robles-Zepeda and Laura A. De la Rosa
Molecules 2022, 27(10), 3154; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27103154 - 14 May 2022
Cited by 3 | Viewed by 1954
Abstract
Tree nuts are rich in polar (phenolic compounds) and non-polar (tocols) antioxidants, with recognized effects in the prevention of diseases such as cancer. These biomolecules possess antiproliferative activity on cancer cells; however, the combined effect of both types of compounds has been scarcely [...] Read more.
Tree nuts are rich in polar (phenolic compounds) and non-polar (tocols) antioxidants, with recognized effects in the prevention of diseases such as cancer. These biomolecules possess antiproliferative activity on cancer cells; however, the combined effect of both types of compounds has been scarcely studied, and this approach could give valuable information on the real anticancer potential of tree nuts. In the present study, the antiproliferative activity of pure tocols and phenolic compounds, tocol- and phenolic-rich extracts (TRE and PRE, respectively) from tree nuts and the extracts combinations, was evaluated in four cancer (HeLa, MCF7, PC3, A549) and one control (ARPE) cell lines. The most sensible cell lines were HeLa and MCF7. TRE and PRE from nuts were chemically characterized; γ and δ tocopherols, total tocols, total tocopherols and total phenolic compounds were negatively correlated with cell viability in MCF7 cells. In HeLa cells, only δ and total tocopherols were negatively correlated with cell viability. TRE and PRE had a low effect in reducing cell viability of the cancer cell lines, the most effective extracts were those of emory oak acorn (EOA), pecan nut (PEC) and walnut (WAL), and these were further studied for their pharmacological interactions, using the combination index and the isobologram methods. Combinations of both extracts showed a synergistic and strongly synergistic behavior in the three nuts (EOA, PEC and WAL), with combination indexes between 0.12 and 0.55. These results highlight the need to understand the interactions among components found in complex natural extracts or food products in order to fully understand their bioactivities. Full article
(This article belongs to the Special Issue New Anticancer Agents Based on Natural Products)
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17 pages, 4753 KiB  
Article
Omega-3 Polyunsaturated Fatty Acids Provoke Apoptosis in Hepatocellular Carcinoma through Knocking Down the STAT3 Activated Signaling Pathway: In Vivo and In Vitro Study
by Noura M. Darwish, Mohamed M. A. Elshaer, Saeedah Musaed Almutairi, Tse-Wei Chen, Mohamed Othman Mohamed, Wael B. A. Ghaly and Rabab Ahmed Rasheed
Molecules 2022, 27(9), 3032; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27093032 - 09 May 2022
Cited by 2 | Viewed by 2101
Abstract
Hepatocellular carcinoma (HCC) is a common type of liver cancer and is a leading cause of death worldwide. Signal transducer and activator of transcription 3 (STAT3) is involved in HCC progression, migration, and suppression of apoptosis. This study investigates the apoptotic effect of [...] Read more.
Hepatocellular carcinoma (HCC) is a common type of liver cancer and is a leading cause of death worldwide. Signal transducer and activator of transcription 3 (STAT3) is involved in HCC progression, migration, and suppression of apoptosis. This study investigates the apoptotic effect of the dietary antioxidant (n-3 PUFAs) on HepG2 cells and analyzes the underlying molecular mechanisms of this effect both in vivo and in vitro. In vivo study: Seventy-five adult male albino rats were divided into three groups (n = 25): Group I (control): 0.9% normal saline, intraperitoneal. Group II: N-Nitrosodiethylamine (200 mg/kg b.wt) intraperitoneal, followed by phenobarbital 0.05% in drinking water. Group III: as group II followed by n-3 PUFAs intubation (400 mg/kg/day). In vivo study: liver specimens for biochemical, histopathological, and immunohistochemical examination. In vitro study: MTT assay, cell morphology, PCR, Western blot, and immunohistochemical analysis. n-3 PUFAs significantly improved the histopathologic features of HCC and decreased the expression of anti-apoptotic proteins. Further, HepG2 cells proliferation was suppressed through inhibition of the STAT3 signaling pathway, cyclin D1, and Bcl-2 activity. Here we report that n-3 PUFAs may be an ideal cancer chemo-preventive candidate by targeting STAT3 signaling, which is involved in cell proliferation and apoptosis. Full article
(This article belongs to the Special Issue New Anticancer Agents Based on Natural Products)
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Review

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19 pages, 1530 KiB  
Review
Therapeutic Role of Alkaloids and Alkaloid Derivatives in Cancer Management
by Kolawole Olofinsan, Heidi Abrahamse and Blassan P. George
Molecules 2023, 28(14), 5578; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules28145578 - 22 Jul 2023
Cited by 10 | Viewed by 3293
Abstract
Cancer is a neoplastic disease that remains a global challenge with a reported prevalence that is increasing annually. Though existing drugs can be applied as single or combined therapies for managing this pathology, their concomitant adverse effects in human applications have led to [...] Read more.
Cancer is a neoplastic disease that remains a global challenge with a reported prevalence that is increasing annually. Though existing drugs can be applied as single or combined therapies for managing this pathology, their concomitant adverse effects in human applications have led to the need to continually screen natural products for effective and alternative anticancer bioactive principles. Alkaloids are chemical molecules that, due to their structural diversity, constitute a reserve for the discovery of lead compounds with interesting pharmacological activities. Several in vitro studies and a few in vivo findings have documented various cytotoxic and antiproliferative properties of alkaloids. This review describes chaetocochin J, neopapillarine, coclaurine, reflexin A, 3,10-dibromofascaplysin and neferine, which belong to different alkaloid classes with antineoplastic properties and have been identified recently from plants. Despite their low solubility and bioavailability, plant-derived alkaloids have viable prospects as sources of viable lead antitumor agents. This potential can be achieved if more research on these chemical compounds is directed toward investigating ways of improving their delivery in an active form close to target cells, preferably with no effect on neighboring normal tissues. Full article
(This article belongs to the Special Issue New Anticancer Agents Based on Natural Products)
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13 pages, 1118 KiB  
Review
Promising Effects of N-Docosahexaenoyl Ethanolamine in Breast Cancer: Molecular and Cellular Insights
by Giuseppina Augimeri and Daniela Bonofiglio
Molecules 2023, 28(9), 3694; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules28093694 - 25 Apr 2023
Cited by 2 | Viewed by 2080
Abstract
Unhealthy dietary habits have been identified as a risk factor for the development and progression of cancer. Therefore, adopting a healthy eating pattern is currently recommended to prevent the onset of different types of cancers, including breast carcinoma. In particular, the Mediterranean diet, [...] Read more.
Unhealthy dietary habits have been identified as a risk factor for the development and progression of cancer. Therefore, adopting a healthy eating pattern is currently recommended to prevent the onset of different types of cancers, including breast carcinoma. In particular, the Mediterranean diet, based on high consumption of omega-3 polyunsaturated fatty acids (N-3 PUFAs), such as those found in cold-water fish and other seafood, nuts, and seeds, is recommended to reduce the incidence of several chronic-degenerative diseases. Indeed, the consumption of N-3 PUFAs, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), reduced the risk of different types of cancer, including breast cancer. Moreover, they can counteract breast cancer progression and reduce the side effects of chemotherapy in breast cancer survival. Studies have demonstrated that DHA, exhibiting greater antitumor activity than EPA in breast cancer, can be attributed to its direct impact on breast cancer cells and also due to its conversion into various metabolites. N-docosahexaenoyl ethanolamine, DHEA, is the most studied DHA derivative for its therapeutic potential in breast cancer. In this review, we emphasize the significance of dietary habits and the consumption of N-3 polyunsaturated fatty acids, particularly DHA, and we describe the current knowledge on the antitumoral action of DHA and its derivative DHEA in the treatment of breast cancer. Full article
(This article belongs to the Special Issue New Anticancer Agents Based on Natural Products)
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20 pages, 2560 KiB  
Review
Exploring the Remarkable Chemotherapeutic Potential of Polyphenolic Antioxidants in Battling Various Forms of Cancer
by Mohammad Imran, Areeba Insaf, Nazeer Hasan, Vrushabh V. Sugandhi, Deumaya Shrestha, Keshav Raj Paudel, Saurav Kumar Jha, Philip M. Hansbro, Kamal Dua, Hari Prasad Devkota and Yousuf Mohammed
Molecules 2023, 28(8), 3475; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules28083475 - 14 Apr 2023
Cited by 8 | Viewed by 2283
Abstract
Plant-derived compounds, specifically antioxidants, have played an important role in scavenging the free radicals present under diseased conditions. The persistent generation of free radicals in the body leads to inflammation and can result in even more severe diseases such as cancer. Notably, the [...] Read more.
Plant-derived compounds, specifically antioxidants, have played an important role in scavenging the free radicals present under diseased conditions. The persistent generation of free radicals in the body leads to inflammation and can result in even more severe diseases such as cancer. Notably, the antioxidant potential of various plant-derived compounds prevents and deregulates the formation of radicals by initiating their decomposition. There is a vast literature demonstrating antioxidant compounds’ anti-inflammatory, anti-diabetic, and anti-cancer potential. This review describes the molecular mechanism of various flavonoids, such as quercetin, kaempferol, naringenin, epicatechin, and epicatechin gallate, against different cancers. Additionally, the pharmaceutical application of these flavonoids against different cancers using nanotechnologies such as polymeric, lipid-based nanoparticles (solid–lipid and liquid–lipid), liposomes, and metallic nanocarriers is addressed. Finally, combination therapies in which these flavonoids are employed along with other anti-cancer agents are described, indicating the effective therapies for the management of various malignancies. Full article
(This article belongs to the Special Issue New Anticancer Agents Based on Natural Products)
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34 pages, 2174 KiB  
Review
The Potential Role of Fisetin, a Flavonoid in Cancer Prevention and Treatment
by Arshad Husain Rahmani, Ahmad Almatroudi, Khaled S. Allemailem, Amjad Ali Khan and Saleh A. Almatroodi
Molecules 2022, 27(24), 9009; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27249009 - 17 Dec 2022
Cited by 12 | Viewed by 5283
Abstract
Cancer is a main culprit and the second-leading cause of death worldwide. The current mode of treatment strategies including surgery with chemotherapy and radiation therapy may be effective, but cancer is still considered a major cause of death. Plant-derived products or their purified [...] Read more.
Cancer is a main culprit and the second-leading cause of death worldwide. The current mode of treatment strategies including surgery with chemotherapy and radiation therapy may be effective, but cancer is still considered a major cause of death. Plant-derived products or their purified bioactive compounds have confirmed health-promoting effects as well as cancer-preventive effects. Among these products, flavonoids belong to polyphenols, chiefly found in fruits, vegetables and in various seeds/flowers. It has been considered to be an effective antioxidant, anti-inflammatory and to play a vital role in diseases management. Besides these activities, flavonoids have been revealed to possess anticancer potential through the modulation of various cell signaling molecules. In this regard, fisetin, a naturally occurring flavonoid, has a confirmed role in disease management through antioxidant, neuro-protective, anti-diabetic, hepato-protective and reno-protective potential. As well, its cancer-preventive effects have been confirmed via modulating various cell signaling pathways including inflammation, apoptosis, angiogenesis, growth factor, transcription factor and other cell signaling pathways. This review presents an overview of the anti-cancer potential of fisetin in different types of cancer through the modulation of cell signaling pathways based on in vivo and in vitro studies. A synergistic effect with anticancer drugs and strategies to improve the bioavailability are described. More clinical trials need to be performed to explore the anti-cancer potential and mechanism-of-action of fisetin and its optimum therapeutic dose. Full article
(This article belongs to the Special Issue New Anticancer Agents Based on Natural Products)
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26 pages, 1371 KiB  
Review
The Multifaceted Role of Baicalein in Cancer Management through Modulation of Cell Signalling Pathways
by Arshad Husain Rahmani, Ahmad Almatroudi, Amjad Ali Khan, Ali Yousif Babiker, Malak Alanezi and Khaled S. Allemailem
Molecules 2022, 27(22), 8023; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27228023 - 18 Nov 2022
Cited by 10 | Viewed by 2816
Abstract
The roles of medicinal plants or their purified bioactive compounds have attracted attention in the field of health sciences due to their low toxicity and minimal side effects. Baicalein is an active polyphenolic compound, isolated from Scutellaria baicalensis, and plays a significant role [...] Read more.
The roles of medicinal plants or their purified bioactive compounds have attracted attention in the field of health sciences due to their low toxicity and minimal side effects. Baicalein is an active polyphenolic compound, isolated from Scutellaria baicalensis, and plays a significant role in the management of different diseases. Epidemiologic studies have proven that there is an inverse association between baicalein consumption and disease severity. Baicalein is known to display anticancer activity through the inhibition of inflammation and cell proliferation. Additionally, the anticancer potential of baicalein is chiefly mediated through the modulation of various cell-signaling pathways, such as the induction of apoptosis, autophagy, cell cycle arrest, inhibition of angiogenesis, signal transducer and activator of transcription 3, and PI3K/Akt pathways, as well as the regulation of other molecular targets. Therefore, the current review aimed to explore the role of baicalein in different types of cancer along with mechanisms of action. Besides this, the synergistic effects with other anti-cancerous drugs and the nano-formulation based delivery of baicalein have also been discussed. Full article
(This article belongs to the Special Issue New Anticancer Agents Based on Natural Products)
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27 pages, 5446 KiB  
Review
Recent Advances in Natural Product-Based Hybrids as Anti-Cancer Agents
by Eleni Sflakidou, George Leonidis, Eirini Foroglou, Christos Siokatas and Vasiliki Sarli
Molecules 2022, 27(19), 6632; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27196632 - 06 Oct 2022
Cited by 11 | Viewed by 3683
Abstract
Cancer is one of the top leading causes of death worldwide. It is a heterogenous disease characterized by unregulated cell proliferation and invasiveness of abnormal cells. For the treatment of cancer, natural products have been widely used as a source of therapeutic ingredients [...] Read more.
Cancer is one of the top leading causes of death worldwide. It is a heterogenous disease characterized by unregulated cell proliferation and invasiveness of abnormal cells. For the treatment of cancer, natural products have been widely used as a source of therapeutic ingredients since ancient times. Although natural compounds and their derivatives have demonstrated strong antitumor activity in many types of cancer, their poor pharmacokinetic properties, low cell selectivity, limited bioavailability and restricted efficacy against drug-resistant cancer cells hinder their wide clinical application. Conjugation of natural products with other bioactive molecules has given rise to a new field in drug discovery resulting to the development of novel, bifunctional and more potent drugs for cancer therapy to overcome the current drawbacks. This review discusses multiple categories of such bifunctional conjugates and highlights recent trends and advances in the development of natural product hybrids. Among them, ADCs, PDCs, ApDCs, PROTACs and AUTOTACs represent emerging therapeutic agents against cancer. Full article
(This article belongs to the Special Issue New Anticancer Agents Based on Natural Products)
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23 pages, 1240 KiB  
Review
Chemistry and the Potential Antiviral, Anticancer, and Anti-Inflammatory Activities of Cardiotonic Steroids Derived from Toads
by Hesham R. El-Seedi, Nermeen Yosri, Bishoy El-Aarag, Shaymaa H. Mahmoud, Ahmed Zayed, Ming Du, Aamer Saeed, Syed G. Musharraf, Islam M. El-Garawani, Mohamed R. Habib, Haroon Elrasheid Tahir, Momtaz M. Hegab, Xiaobo Zou, Zhiming Guo, Thomas Efferth and Shaden A. M. Khalifa
Molecules 2022, 27(19), 6586; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27196586 - 05 Oct 2022
Cited by 8 | Viewed by 2418
Abstract
Cardiotonic steroids (CTS) were first documented by ancient Egyptians more than 3000 years ago. Cardiotonic steroids are a group of steroid hormones that circulate in the blood of amphibians and toads and can also be extracted from natural products such as plants, herbs, [...] Read more.
Cardiotonic steroids (CTS) were first documented by ancient Egyptians more than 3000 years ago. Cardiotonic steroids are a group of steroid hormones that circulate in the blood of amphibians and toads and can also be extracted from natural products such as plants, herbs, and marines. It is well known that cardiotonic steroids reveal effects against congestive heart failure and atrial fibrillation; therefore, the term "cardiotonic" has been coined. Cardiotonic steroids are divided into two distinct groups: cardenolides (plant-derived) and bufadienolides (mainly of animal origin). Cardenolides have an unsaturated five-membered lactone ring attached to the steroid nucleus at position 17; bufadienolides have a doubly unsaturated six-membered lactone ring. Cancer is a leading cause of mortality in humans all over the world. In 2040, the global cancer load is expected to be 28.4 million cases, which would be a 47% increase from 2020. Moreover, viruses and inflammations also have a very nebative impact on human health and lead to mortality. In the current review, we focus on the chemistry, antiviral and anti-cancer activities of cardiotonic steroids from the naturally derived (toads) venom to combat these chronic devastating health problems. The databases of different research engines (Google Scholar, PubMed, Science Direct, and Sci-Finder) were screened using different combinations of the following terms: “cardiotonic steroids”, “anti-inflammatory”, “antiviral”, “anticancer”, “toad venom”, “bufadienolides”, and “poison chemical composition”. Various cardiotonic steroids were isolated from diverse toad species and exhibited superior anti-inflammatory, anticancer, and antiviral activities in in vivo and in vitro models such as marinobufagenin, gammabufotalin, resibufogenin, and bufalin. These steroids are especially difficult to identify. However, several compounds and their bioactivities were identified by using different molecular and biotechnological techniques. Biotechnology is a new tool to fully or partially generate upscaled quantities of natural products, which are otherwise only available at trace amounts in organisms. Full article
(This article belongs to the Special Issue New Anticancer Agents Based on Natural Products)
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33 pages, 2150 KiB  
Review
The Potential Role of Apigenin in Cancer Prevention and Treatment
by Arshad Husain Rahmani, Mohammed A. Alsahli, Ahmad Almatroudi, Mashael Abdullah Almogbel, Amjad Ali Khan, Shehwaz Anwar and Saleh A. Almatroodi
Molecules 2022, 27(18), 6051; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27186051 - 16 Sep 2022
Cited by 39 | Viewed by 5672
Abstract
Cancer is the leading cause of death worldwide. In spite of advances in the treatment of cancer, currently used treatment modules including chemotherapy, hormone therapy, radiation therapy and targeted therapy causes adverse effects and kills the normal cells. Therefore, the goal of more [...] Read more.
Cancer is the leading cause of death worldwide. In spite of advances in the treatment of cancer, currently used treatment modules including chemotherapy, hormone therapy, radiation therapy and targeted therapy causes adverse effects and kills the normal cells. Therefore, the goal of more effective and less side effects-based cancer treatment approaches is still at the primary position of present research. Medicinal plants or their bioactive ingredients act as dynamic sources of drugs due to their having less side effects and also shows the role in reduction of resistance against cancer therapy. Apigenin is an edible plant-derived flavonoid that has received significant scientific consideration for its health-promoting potential through modulation of inflammation, oxidative stress and various other biological activities. Moreover, the anti-cancer potential of apigenin is confirmed through its ability to modulate various cell signalling pathways, including tumor suppressor genes, angiogenesis, apoptosis, cell cycle, inflammation, apoptosis, PI3K/AKT, NF-κB, MAPK/ERK and STAT3 pathways. The current review mainly emphases the potential role of apigenin in different types of cancer through the modulation of various cell signaling pathways. Further studies based on clinical trials are needed to explore the role of apigenin in cancer management and explain the possible potential mechanisms of action in this vista. Full article
(This article belongs to the Special Issue New Anticancer Agents Based on Natural Products)
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