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Anticancer Properties of Natural and Derivative Products II

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A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Natural Products Chemistry".

Deadline for manuscript submissions: closed (31 July 2022) | Viewed by 24588

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Special Issue Editors

Prof. Dr. José Antonio Lupiáñez

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Department of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada, Avenida Fuentenueva 1, 18071 Granada, Spain
Interests: study of the anticancer potential of natural and derivatives products derived from the olive grove; molecular pathways involved in anticancer processes; glucose metabolism and its regulation; enzimology and kinetics; biochemical characterization of anti-inflammatory and anti-oxidant properties; proteomics and metabolomics associated with cancer; cell growth processes: protein synthesis and degradation
Special Issues, Collections and Topics in MDPI journals

Dr. Eva E. Rufino Palomares

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Department of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada, 18012 Granada, Spain
Interests: anticancer bioactivities of natural products; functional proteomics; gene regulation by microRNAs; molecular characterization during inflammation and oxidative stress
Special Issues, Collections and Topics in MDPI journals

Dr. Amalia Pérez-Jiménez

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Guest Editor

Department of Zoology, University of Granada, 18012 Granada, Spain
Interests: animal welfare; aquatic toxicology; functional molecules; natural compounds; oxidative stress and immunology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear colleagues,

This Special Issue continues from Volume I, and its main objective is to collect and disseminate significant and recent contributions on the use of natural compounds and their chemical derivatives capable of significantly modifying their intrinsic biological activities, especially those aimed at the prevention and treatment of all kinds of diseases. The content of this new volume also extends to those inorganic compounds that present the different biological capacities that are detailed below.

Both the natural compounds synthesized by plants, microorganisms, or terrestrial and marine animals as well as their chemical derivatives in addition to the inorganic compounds synthesized in the laboratory must demonstrate clear, significant, and novel biological activity. In the case of natural compounds, we know that they have been used in different cultures for the prevention and treatment of various human diseases.

For those submitted papers in which extracts from different biological sources are used, it is expressly recommended that the authors always include an exhaustive analysis of the main component compounds. In other words, the papers submitted on the biological activity of natural extracts will only be considered if they are accompanied by adequate chemical characterization.

Among the biological properties that are especially requested on this occasion are analgesic, anti-allodynic, antidiabetic, antioxidant, antiparasitic, antimicrobial, antiviral, anti-atherogenic, anti-inflammatory, antiproliferative, antitumor, and growth-stimulating activities as well as cardio- and neuroprotective activities.

In this new volume, special attention is paid to the study of antitumor capacity through the potential modulation of cancer initiation and growth, cell differentiation, apoptosis and autophagy, angiogenesis, and metastatic spread as well as the molecular mechanisms that sustain these processes.

Prof. Dr. José Antonio Lupiáñez
Dr. Eva E. Rufino-Palomares
Dr. Amalia Pérez-Jiménez
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

angiogenesis
cancer
chemoprevention
inflammation
molecular pathways
natural and derivative products
oxidative stress

Published Papers (8 papers)

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Research

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18 pages, 2886 KiB

Open AccessArticle

Co-Application of Statin and Flavonoids as an Effective Strategy to Reduce the Activity of Voltage-Gated Potassium Channels Kv1.3 and Induce Apoptosis in Human Leukemic T Cell Line Jurkat

by Andrzej Teisseyre, Mateusz Chmielarz, Anna Uryga, Kamila Środa-Pomianek and Anna Palko-Łabuz

Molecules 2022, 27(10), 3227; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27103227 - 18 May 2022

Cited by 6 | Viewed by 2058

Abstract

Voltage-gated potassium channels of the Kv1.3 type are considered a potential new molecular target in several pathologies, including some cancer disorders and COVID-19. Lipophilic non-toxic organic inhibitors of Kv1.3 channels, such as statins and flavonoids, may have clinical applications in supporting the therapy of some cancer diseases, such as breast, pancreas, and lung cancer; melanoma; or chronic lymphocytic leukemia. This study focuses on the influence of the co-application of statins—simvastatin (SIM) or mevastatin (MEV)—with flavonoids 8-prenylnaringenin (8-PN), 6-prenylnarigenin (6-PN), xanthohumol (XANT), acacetin (ACAC), or chrysin on the activity of Kv1.3 channels, viability, and the apoptosis of cancer cells in the human T cell line Jurkat. We showed that the inhibitory effect of co-application of the statins with flavonoids was significantly more potent than the effects exerted by each compound applied alone. Combinations of simvastatin with chrysin, as well as mevastatin with 8-prenylnaringenin, seem to be the most promising. We also found that these results correlate with an increased ability of the statin–flavonoid combination to reduce viability and induce apoptosis in cancer cells compared to single compounds. Our findings suggest that the co-application of statins and flavonoids at low concentrations may increase the effectiveness and safety of cancer therapy. Thus, the simultaneous application of statins and flavonoids may be a new and promising anticancer strategy. Full article

(This article belongs to the Special Issue Anticancer Properties of Natural and Derivative Products II)

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17 pages, 1057 KiB

Open AccessArticle

Scalable Synthesis and Cancer Cell Cytotoxicity of Rooperol and Analogues

by Zachary T. Schwartz, Peter D. Theisen, Olaf T. Bjornstal, Mary Rodebaugh, Mauricio A. Jemal, Dallas Lee, Spencer D. Shelton, Zhenze Zhao, Liqin Du and Sean M. Kerwin

Molecules 2022, 27(6), 1792; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27061792 - 09 Mar 2022

Cited by 1 | Viewed by 3132

Abstract

Plant polyphenols, such as the African potato (Hypoxis hemerocallidea)-derived bis-catechol rooperol, can display promising anticancer activity yet suffer from rapid metabolism. Embarking upon a program to systematically examine potentially more metabolically stable replacements for the catechol rings in rooperol, we report here a general, scalable synthesis of rooperol and analogues that builds on our previous synthetic approach incorporating a key Pd-catalyzed decarboxylative coupling strategy. Using this approach, we have prepared and evaluated the cancer cell cytotoxicity of rooperol and a series of analogues. While none of the analogues examined here were superior to rooperol in preventing the growth of cancer cells, analogues containing phenol or methylenedioxyphenyl replacements for one or both catechol rings were nearly as effective as rooperol. Full article

(This article belongs to the Special Issue Anticancer Properties of Natural and Derivative Products II)

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16 pages, 2744 KiB

Open AccessArticle

A Novel Docetaxel-Biotin Chemical Conjugate for Prostate Cancer Treatment

by Mahmoud Rayan, Seba Shadafny, Adam Falah, Mizied Falah, Saleh Abu-Lafi, Sare Asli and Anwar Rayan

Molecules 2022, 27(3), 961; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27030961 - 31 Jan 2022

Cited by 6 | Viewed by 2968

Abstract

A novel conjugate of docetaxel and biotin (designated as IDD-1010) was designed and chemically synthesized via an ester linkage at position 2’ carbon in docetaxel. The synthesized pure IDD-1010 exhibits a potent anti-cancer activity in in vitro and in vivo studies. At 10 nM, IDD-1010 has induced increased apoptosis and mitotic arrest of PC3-Luc prostate cancer cells, causing aneuploidy and cell death at higher concentrations. Toxicology studies indicate that the maximal tolerated dose (MTD) of IDD-1010 is 150 mg/kg in mice; equivalent to about 12.2 mg/kg of body weight, or to about an 850 mg dose for a patient weighing 70 kg. The MTD-treated mice exhibited weight gain similar to that of the control group, with no gross pathological signs at 14 days post-dosing. At a lower dose, IDD-1010 treatment did not lead to any significant weight loss in mice, although decreased the tumor volume stemming from injecting cancer cells into the dorsal loop of mouse prostate, and it was found to be more potent than Paclitaxel (reference drug). Similarly, IDD-1010 treatment significantly reduced tumor weight and thereby increased the percentage of mice survival as compared to reference drug-treated and control groups. To summarize, the described experiments using IDD-1010, as compared to the reference drug, strongly suggest a potential treatment utility with a wider therapeutic window for prostate cancer. Henceforth, clinical research on such a novel drug candidate would be greatly worthwhile. Full article

(This article belongs to the Special Issue Anticancer Properties of Natural and Derivative Products II)

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22 pages, 2516 KiB

Open AccessArticle

Anticancer Effects and Molecular Action of 7-α-Hydroxyfrullanolide in G2/M-Phase Arrest and Apoptosis in Triple Negative Breast Cancer Cells

by Siriphorn Chimplee, Sittiruk Roytrakul, Suchada Sukrong, Theera Srisawat, Potchanapond Graidist and Kanyanatt Kanokwiroon

Molecules 2022, 27(2), 407; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27020407 - 09 Jan 2022

Cited by 7 | Viewed by 2927

Abstract

Triple negative breast cancer (TNBC) is a breast cancer subtype characterized by the absence of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 expression. TNBC cells respond poorly to targeted chemotherapies currently in use and the mortality rate of TNBC remains high. Therefore, it is necessary to identify new chemotherapeutic agents for TNBC. In this study, the anti-cancer effects of 7-α-hydroxyfrullanolide (7HF), derived from Grangea maderaspatana, on MCF-7, MDA-MB-231 and MDA-MB-468 breast cancer cells were assessed using MTT assay. The mode of action of 7HF in TNBC cells treated with 6, 12 and 24 µM of 7HF was determined by flow cytometry and propidium iodide (PI) staining for cell cycle analysis and annexin V/fluorescein isothiocyanate + PI staining for detecting apoptosis. The molecular mechanism of action of 7HF in TNBC cells was investigated by evaluating protein expression using proteomic techniques and western blotting. Subsequently, 7HF exhibited the strongest anti-TNBC activity toward MDA-MB-468 cells and a concomitantly weak toxicity toward normal breast cells. The molecular mechanism of action of low-dose 7HF in TNBC cells primarily involved G2/M-phase arrest through upregulation of the expression of Bub3, cyclin B1, phosphorylated Cdk1 (Tyr 15) and p53-independent p21. Contrastingly, the upregulation of PP2A-A subunit expression may have modulated the suppression of various cell survival proteins such as p-Akt (Ser 473), FoxO3a and β-catenin. The concurrent apoptotic effect of 7HF on the treated cells was mediated via both intrinsic and extrinsic modes through the upregulation of Bax and active cleaved caspase-7–9 expression and downregulation of Bcl-2 and full-length caspase-7–9 expression. Notably, the proteomic approach revealed the upregulation of the expression of pivotal protein clusters associated with G1/S-phase arrest, G2/M-phase transition and apoptosis. Thus, 7HF exhibits promising anti-TNBC activity and at a low dose, it modulates signal transduction associated with G2/M-phase arrest and apoptosis. Full article

(This article belongs to the Special Issue Anticancer Properties of Natural and Derivative Products II)

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11 pages, 1594 KiB

Open AccessArticle

Luteolin Inhibits Breast Cancer Stemness and Enhances Chemosensitivity through the Nrf2-Mediated Pathway

by Kuen-Jang Tsai, Hsin-Yi Tsai, Chin-Chuan Tsai, Tai-Yu Chen, Tsung-Hua Hsieh, Chun-Lin Chen, Lulekiwe Mbuyisa, Yaw-Bin Huang and Ming-Wei Lin

Molecules 2021, 26(21), 6452; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26216452 - 26 Oct 2021

Cited by 45 | Viewed by 3020

Abstract

Cancer stem cells (CSCs) are subpopulations of tumor masses with unique abilities in self-renewal, stemness maintenance, drug resistance, and the promotion of cancer recurrence. Recent studies have suggested that breast CSCs play essential roles in chemoresistance. Therefore, new agents that selectively target such cells are urgently required. Reactive oxygen species (ROS)-producing enzymes are the reason for an elevated tumor oxidant status. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcriptional factor, which upon detecting cellular oxidative stress, binds to the promoter region of antioxidant genes. By triggering a cytoprotective response, Nrf2 maintains cellular redox status. Cripto-1 participates in the self-renewal of CSCs. Herein, luteolin, a flavonoid found in Taraxacum officinale extract, was determined to inhibit the expressions of stemness-related transcriptional factors, the ATP-binding cassette transporter G2 (ABCG2), CD44, aldehyde dehydrogenase 1 activity as well as the sphere formation properties of breast CSCs. Furthermore, luteolin suppressed the protein expressions of Nrf2, heme oxygenase 1 (HO-1), and Cripto-1 which have been determined to contribute critically to CSC features. The combination of luteolin and the chemotherapeutic drug, Taxol, resulted in enhanced cytotoxicity to breast cancer cells. These findings suggest that luteolin treatment significantly attenuated the hallmarks of breast cancer stemness by downregulating Nrf2-mediated expressions. Luteolin constitutes a potential agent for use in cancer stemness-targeted breast cancer treatments. Full article

(This article belongs to the Special Issue Anticancer Properties of Natural and Derivative Products II)

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16 pages, 4836 KiB

Open AccessArticle

Betulinic Acid Modulates the Expression of HSPA and Activates Apoptosis in Two Cell Lines of Human Colorectal Cancer

by Laphatrada Yurasakpong, Chanin Nantasenamat, Saksit Nobsathian, Kulathida Chaithirayanon and Somjai Apisawetakan

Molecules 2021, 26(21), 6377; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26216377 - 22 Oct 2021

Cited by 2 | Viewed by 1875

Abstract

Betulinic acid (BA) is a pentacyclic triterpene usually isolated from botanical sources. Numerous studies have reported the inhibitory effect of BA against human colorectal cancer cells (CRC). However, its effect on the expression of the molecular chaperone HSPA is unclear. The aim of this research is to investigate the anti-cancer activities of BA purified from Piper retrofractum and study its effect on the expression of HSPA in colorectal cancer HCT116 and SW480 cells. The viability of both cancer cells was reduced after they were treated with an increasing dosage of BA. Flow cytometry assay revealed that levels of cell apoptosis significantly increased after incubation with BA in both cancer cells. Pro-apoptotic markers including Bax, cleaved-caspase-3 and cleaved-caspase-9 were increased while anti-apoptotic marker Bcl-2 was decreased after BA treatment. Western blot also showed that the expression of HSPA fluctuated upon BA treatment, whereby HSPA was increased at lower BA concentrations while at higher BA concentrations HSPA expression was decreased. Preliminary molecular docking assay showed that BA can bind to the nucleotide binding domain of the HSP70 at its ADP-bound state of the HSP70. Although further research is needed to comprehend the BA-HSPA interaction, our findings indicate that BA can be considered as potential candidate for the development of new treatment for colorectal cancer. Full article

(This article belongs to the Special Issue Anticancer Properties of Natural and Derivative Products II)

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Review

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29 pages, 3313 KiB

Open AccessReview

Nutraceutical Role of Polyphenols and Triterpenes Present in the Extracts of Fruits and Leaves of Olea europaea as Antioxidants, Anti-Infectives and Anticancer Agents on Healthy Growth

by Eva E. Rufino-Palomares, Amalia Pérez-Jiménez, Leticia García-Salguero, Khalida Mokhtari, Fernando J. Reyes-Zurita, Juan Peragón-Sánchez and José A. Lupiáñez

Molecules 2022, 27(7), 2341; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27072341 - 05 Apr 2022

Cited by 27 | Viewed by 3678

Abstract

There is currently a worldwide consensus and recognition of the undoubted health benefits of the so-called Mediterranean diet, with its intake being associated with a lower risk of mortality. The most important characteristics of this type of diet are based on the consumption of significant amounts of fruit, vegetables, legumes, and nuts, which provide, in addition to some active ingredients, fiber and a proportion of vegetable protein, together with extra virgin olive oil (EVOO) as the main sources of vegetable fat. Fish and meat from poultry and other small farm animals are the main sources of protein. One of the main components, as already mentioned, is EVOO, which is rich in monounsaturated fatty acids and to a lesser extent in polyunsaturated fatty acids. The intake of this type of nutrient also provides an important set of phytochemicals whose health potential is widely spread and agreed upon. These phytochemicals include significant amounts of anthocyanins, stilbenes, flavonoids, phenolic acids, and terpenes of varying complexities. Therefore, the inclusion in the diet of this type of molecules, with a proven healthy effect, provides an unquestionable preventive and/or curative activity on an important group of pathologies related to cardiovascular, infectious, and cancerous diseases, as well as those related to the metabolic syndrome. The aim of this review is therefore to shed light on the nutraceutical role of two of the main phytochemicals present in Olea europaea fruit and leaf extracts, polyphenols, and triterpenes, on healthy animal growth. Their immunomodulatory, anti-infective, antioxidant, anti-aging, and anti-carcinogenic capabilities show them to be potential nutraceuticals, providing healthy growth. Full article

(This article belongs to the Special Issue Anticancer Properties of Natural and Derivative Products II)

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26 pages, 11233 KiB

Open AccessReview

Alkaloids and Colon Cancer: Molecular Mechanisms and Therapeutic Implications for Cell Cycle Arrest

by Haroon Khan, Waqas Alam, Khalaf F. Alsharif, Michael Aschner, Samreen Pervez and Luciano Saso

Molecules 2022, 27(3), 920; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27030920 - 28 Jan 2022

Cited by 16 | Viewed by 3945

Abstract

Cancer is the second most fatal disease worldwide, with colon cancer being the third most prevalent and fatal form of cancer in several Western countries. The risk of acquisition of resistance to chemotherapy remains a significant hurdle in the management of various types of cancer, especially colon cancer. Therefore, it is essential to develop alternative treatment modalities. Naturally occurring alkaloids have been shown to regulate various mechanistic pathways linked to cell proliferation, cell cycle, and metastasis. This review aims to shed light on the potential of alkaloids as anti-colon-cancer chemotherapy agents that can modulate or arrest the cell cycle. Preclinical investigated alkaloids have shown anti-colon cancer activities and inhibition of cancer cell proliferation via cell cycle arrest at different stages, suggesting that alkaloids may have the potential to act as anticancer molecules. Full article

(This article belongs to the Special Issue Anticancer Properties of Natural and Derivative Products II)

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