Editorial

3 pages, 175 KiB

Open AccessEditorial

Innovation through Tradition: The Current Challenges in Cancer Treatment

by Luigi Sapio and Silvio Naviglio

Int. J. Mol. Sci. 2022, 23(10), 5296; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23105296 - 10 May 2022

Cited by 4 | Viewed by 1357

Despite the huge efforts in identifying novel risk factors, earlier diagnostic markers and alternative therapeutic approaches, malignant disorders continue to pose the second leading cause of death worldwide [...] Full article

(This article belongs to the Special Issue Innovation through Tradition: The Current Challenges in Cancer Treatment)

Research

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15 pages, 3735 KiB

Open AccessArticle

Identification of Spiro-Fused Pyrrolo[3,4-a]pyrrolizines and Tryptanthrines as Potential Antitumor Agents: Synthesis and In Vitro Evaluation

by Diana K. Latypova, Stanislav V. Shmakov, Sofya A. Pechkovskaya, Alexander S. Filatov, Alexander V. Stepakov, Nickolay A. Knyazev and Vitali M. Boitsov

Int. J. Mol. Sci. 2021, 22(21), 11997; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222111997 - 05 Nov 2021

Cited by 8 | Viewed by 1681

Abstract

A series of heterocyclic compounds containing a spiro-fused pyrrolo[3,4-a]pyrrolizine and tryptanthrin framework have been synthesized and studied as potential antitumor agents. Cytotoxicity of products was screened against human erythroleukemia (K562) and human cervical carcinoma (HeLa) cell lines. Among the screened compounds. [...] Read more.

A series of heterocyclic compounds containing a spiro-fused pyrrolo[3,4-a]pyrrolizine and tryptanthrin framework have been synthesized and studied as potential antitumor agents. Cytotoxicity of products was screened against human erythroleukemia (K562) and human cervical carcinoma (HeLa) cell lines. Among the screened compounds. 4a, 4b and 5a were active against human erythroleukemia (K562) cell line, while 4a and 5a were active against cervical carcinoma (HeLa) cell line. In agreement with the DNA cytometry studies, the tested compounds have achieved significant cell-cycle perturbation with higher accumulation of cells in G2/M phase and induced apoptosis. Using confocal microscopy, we found that with 4a and 5a treatment of HeLa cells, actin filaments disappeared, and granular actin was distributed diffusely in the cytoplasm in 76–91% of cells. We discovered that HeLa cells after treatment with compounds 4a and 5a significantly reduced the number of cells with filopodium-like membrane protrusions (from 63 % in control cells to 29% after treatment) and a decrease in cell motility. Full article

(This article belongs to the Special Issue Innovation through Tradition: The Current Challenges in Cancer Treatment)

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16 pages, 2747 KiB

Open AccessArticle

Chlorogenic Acid Enhances Doxorubicin-Mediated Cytotoxic Effect in Osteosarcoma Cells

by Alessia Salzillo, Angela Ragone, Annamaria Spina, Silvio Naviglio and Luigi Sapio

Int. J. Mol. Sci. 2021, 22(16), 8586; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22168586 - 10 Aug 2021

Cited by 18 | Viewed by 1957

Abstract

Despite the recurring outbreak of resistance mechanisms and adverse reactions, doxorubicin (Doxo) still remains the standard-of-care for several cancers, including osteosarcoma (OS). As an appealing source of phytochemical compounds, naturally occurring molecules have extensively been reported to overcome Doxo limitations in preclinical models. [...] Read more.

Despite the recurring outbreak of resistance mechanisms and adverse reactions, doxorubicin (Doxo) still remains the standard-of-care for several cancers, including osteosarcoma (OS). As an appealing source of phytochemical compounds, naturally occurring molecules have extensively been reported to overcome Doxo limitations in preclinical models. Unlike other dietary polyphenols, only few studies recognize chlorogenic acid (CGA) as a potential partner in combination therapy, while, conversely, its anticancer evidence is steadily growing, ultimately in OS. On this basis, herein we examine the cooperating effects between CGA and Doxo in U2OS and MG-63 human OS cells. With respect to Doxo alone, the concomitant administration of CGA further decreased cell viability and growth, promoting cell death potentially via apoptosis induction. Furthermore, a longer-lasting reduction in clonogenic potential deeply supported the CGA ability to improve Doxo efficacy in those cells. Remarkably, CGA treatment ameliorated Doxo-induced cytotoxicity in H9c2 rat cardiomyocyte cells instead. Although inactivation of p44/42 MAPK was detected in response to CGA plus Doxo, PD98059-mediated p44/42 MAPK impairment enhanced the combination outcome in OS cells. These findings firstly propose CGA as a promising chemosensitizer and cardioprotective agent in OS therapy, suggesting the p44/42 MAPK pathway as relevantly involved in CGA-mediated Doxo susceptibility. Full article

(This article belongs to the Special Issue Innovation through Tradition: The Current Challenges in Cancer Treatment)

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17 pages, 19890 KiB

Open AccessArticle

Metabolic Fingerprinting of Murine L929 Fibroblasts as a Cell-Based Tumour Suppressor Model System for Methionine Restriction

by Werner Schmitz, Corinna Koderer, Mohamed El-Mesery, Sebastian Gubik, Rene Sampers, Anton Straub, Alexander Christian Kübler and Axel Seher

Int. J. Mol. Sci. 2021, 22(6), 3039; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22063039 - 16 Mar 2021

Cited by 2 | Viewed by 2341

Abstract

Since Otto Warburg reported in 1924 that cancer cells address their increased energy requirement through a massive intake of glucose, the cellular energy level has offered a therapeutic anticancer strategy. Methionine restriction (MetR) is one of the most effective approaches for inducing low-energy [...] Read more.

Since Otto Warburg reported in 1924 that cancer cells address their increased energy requirement through a massive intake of glucose, the cellular energy level has offered a therapeutic anticancer strategy. Methionine restriction (MetR) is one of the most effective approaches for inducing low-energy metabolism (LEM) due to the central position in metabolism of this amino acid. However, no simple in vitro system for the rapid analysis of MetR is currently available, and this study establishes the murine cell line L929 as such a model system. L929 cells react rapidly and efficiently to MetR, and the analysis of more than 150 different metabolites belonging to different classes (amino acids, urea and tricarboxylic acid cycle (TCA) cycles, carbohydrates, etc.) by liquid chromatography/mass spectrometry (LC/MS) defines a metabolic fingerprint and enables the identification of specific metabolites representing normal or MetR conditions. The system facilitates the rapid and efficient testing of potential cancer therapeutic metabolic targets. To date, MS studies of MetR have been performed using organisms and yeast, and the current LC/MS analysis of the intra- and extracellular metabolites in the murine cell line L929 over a period of 5 days thus provides new insights into the effects of MetR at the cellular metabolic level. Full article

(This article belongs to the Special Issue Innovation through Tradition: The Current Challenges in Cancer Treatment)

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Review

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25 pages, 3979 KiB

Open AccessReview

The Influence of Cell Cycle Regulation on Chemotherapy

by Ying Sun, Yang Liu, Xiaoli Ma and Hao Hu

Int. J. Mol. Sci. 2021, 22(13), 6923; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22136923 - 28 Jun 2021

Cited by 104 | Viewed by 8425

Abstract

Cell cycle regulation is orchestrated by a complex network of interactions between proteins, enzymes, cytokines, and cell cycle signaling pathways, and is vital for cell proliferation, growth, and repair. The occurrence, development, and metastasis of tumors are closely related to the cell cycle. [...] Read more.

Cell cycle regulation is orchestrated by a complex network of interactions between proteins, enzymes, cytokines, and cell cycle signaling pathways, and is vital for cell proliferation, growth, and repair. The occurrence, development, and metastasis of tumors are closely related to the cell cycle. Cell cycle regulation can be synergistic with chemotherapy in two aspects: inhibition or promotion. The sensitivity of tumor cells to chemotherapeutic drugs can be improved with the cooperation of cell cycle regulation strategies. This review presented the mechanism of the commonly used chemotherapeutic drugs and the effect of the cell cycle on tumorigenesis and development, and the interaction between chemotherapy and cell cycle regulation in cancer treatment was briefly introduced. The current collaborative strategies of chemotherapy and cell cycle regulation are discussed in detail. Finally, we outline the challenges and perspectives about the improvement of combination strategies for cancer therapy. Full article

(This article belongs to the Special Issue Innovation through Tradition: The Current Challenges in Cancer Treatment)

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22 pages, 1887 KiB

Open AccessReview

Tumor-Associated Macrophages as Multifaceted Regulators of Breast Tumor Growth

by Maliha Tabassum Munir, Matthew K. Kay, Min H. Kang, Md Mizanur Rahman, Ahmed Al-Harrasi, Mahua Choudhury, Naima Moustaid-Moussa, Fazle Hussain and Shaikh Mizanoor Rahman

Int. J. Mol. Sci. 2021, 22(12), 6526; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22126526 - 18 Jun 2021

Cited by 64 | Viewed by 10302

Abstract

Breast cancer is the most commonly occurring cancer in women of Western countries and is the leading cause of cancer-related mortality. The breast tumor microenvironment contains immune cells, fibroblasts, adipocytes, mesenchymal stem cells, and extracellular matrix. Among these cells, macrophages or tumor-associated macrophages [...] Read more.

Breast cancer is the most commonly occurring cancer in women of Western countries and is the leading cause of cancer-related mortality. The breast tumor microenvironment contains immune cells, fibroblasts, adipocytes, mesenchymal stem cells, and extracellular matrix. Among these cells, macrophages or tumor-associated macrophages (TAMs) are the major components of the breast cancer microenvironment. TAMs facilitate metastasis of the breast tumor and are responsible for poor clinical outcomes. High TAM density was also found liable for the poor prognosis of breast cancer. These observations make altering TAM function a potential therapeutic target to treat breast cancer. The present review summarizes the origin of TAMs, mechanisms of macrophage recruitment and polarization in the tumor, and the contributions of TAMs in tumor progression. We have also discussed our current knowledge about TAM-targeted therapies and the roles of miRNAs and exosomes in re-educating TAM function. Full article

(This article belongs to the Special Issue Innovation through Tradition: The Current Challenges in Cancer Treatment)

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20 pages, 8135 KiB

Open AccessReview

Application of Nano-Drug Delivery System Based on Cascade Technology in Cancer Treatment

by Ying Sun, Xiaoli Ma and Hao Hu

Int. J. Mol. Sci. 2021, 22(11), 5698; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22115698 - 27 May 2021

Cited by 27 | Viewed by 4982

Abstract

In the current cancer treatment, various combination therapies have been widely used, such as photodynamic therapy (PDT) combined with chemokinetic therapy (CDT). However, due to the complexity of the tumor microenvironment (TME) and the limitations of treatment, the efficacy of current treatment options [...] Read more.

In the current cancer treatment, various combination therapies have been widely used, such as photodynamic therapy (PDT) combined with chemokinetic therapy (CDT). However, due to the complexity of the tumor microenvironment (TME) and the limitations of treatment, the efficacy of current treatment options for some cancers is unsatisfactory. Nowadays, cascade technology has been used in cancer treatment and achieved good therapeutic effect. Cascade technology based on nanotechnology can trigger cascade reactions under specific tumor conditions to achieve precise positioning and controlled release, or amplify the efficacy of each drug to improve anticancer efficacy and reduce side effects. Compared with the traditional treatment, the application of cascade technology has achieved the controllability, specificity, and effectiveness of cancer treatment. This paper reviews the application of cascade technology in drug delivery, targeting, and release via nano-drug delivery systems in recent years, and introduces their application in reactive oxygen species (ROS)-induced cancer treatment. Finally, we briefly describe the current challenges and prospects of cascade technology in cancer treatment in the future. Full article

(This article belongs to the Special Issue Innovation through Tradition: The Current Challenges in Cancer Treatment)

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17 pages, 1461 KiB

Open AccessReview

Natural Compounds as Therapeutic Agents: The Case of Human Topoisomerase IB

by Alessio Ottaviani, Federico Iacovelli, Paola Fiorani and Alessandro Desideri

Int. J. Mol. Sci. 2021, 22(8), 4138; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22084138 - 16 Apr 2021

Cited by 14 | Viewed by 2372

Abstract

Natural products are widely used as source for drugs development. An interesting example is represented by natural drugs developed against human topoisomerase IB, a ubiquitous enzyme involved in many cellular processes where several topological problems occur due the formation of supercoiled DNA. Human [...] Read more.

Natural products are widely used as source for drugs development. An interesting example is represented by natural drugs developed against human topoisomerase IB, a ubiquitous enzyme involved in many cellular processes where several topological problems occur due the formation of supercoiled DNA. Human topoisomerase IB, involved in the solution of such problems relaxing the DNA cleaving and religating a single DNA strand, represents an important target in anticancer therapy. Several natural compounds inhibiting or poisoning this enzyme are under investigation as possible new drugs. This review summarizes the natural products that target human topoisomerase IB that may be used as the lead compounds to develop new anticancer drugs. Moreover, the natural compounds and their derivatives that are in clinical trial are also commented on. Full article

(This article belongs to the Special Issue Innovation through Tradition: The Current Challenges in Cancer Treatment)

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