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Pharmaceuticals
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Multidrug Resistance in Cancer: Pharmacological Strategies
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Multidrug Resistance in Cancer: Pharmacological Strategies

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 3770

Special Issue Editor

Prof. Dr. Chin-Chuan Hung

E-Mail Website
Guest Editor
Department of Pharmacy, College of Pharmacy, China Medical University, 91 Hsueh-Shih Road, Taichung 40402, Taiwan
Interests: cancer; multidrug resistance; pharmacogenomics

Special Issue Information

Dear Colleagues,

Multidrug resistance is one of the major obstacles in current cancer treatment. Various mechanisms have been proposed for the development of drug resistance in cancers, such as heterogeneity of cancer cells, changes of cellular levels, overexpression of ABC transporters, ROS related pathways, as well as cancer stem cells development. To overcome the multidrug resistance in cancer treatment, small molecules, natural products, peptides, and nanotherapeutics have been developed in recent years. The most explored therapeutic target for combating multidrug resistance cancer is P-glycoprotein (P-gp), which belongs to the ABC transporter family. In addition, multidrug resistant cancer cells show selective sensitivity (collateral sensitivity) to some compounds, such as verapamil, danazol, etc. It has been proposed that P-gp-overexpressing cells are more sensitive to increased reactive oxygen species, to agents interfering the metabolic pathways related to cellular energy, and to alteration of membrane composition, and that they influence the elimination of endogenous toxic catabolites. However, the underlying mechanisms of collateral sensitivity have not been fully evaluated. This Special Issue welcomes studies, including original articles and reviews that investigate pharmacological strategies to overcome multidrug resistance in cancer treatment, ranging from basic research to clinical studies.

Prof. Dr. Chin-Chuan Hung
Guest Editor

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. Pharmaceuticals is an international peer-reviewed open access monthly 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 2900 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

  • cancer
  • multidrug resistance
  • P-glycoprotein
  • MRP1
  • BCRP
  • ABC transporters
  • collateral sensitivity
  • cancer stem cells

Published Papers (2 papers)

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Research

22 pages, 5271 KiB  
Article
Pinostrobin and Tectochrysin Conquer Multidrug-Resistant Cancer Cells via Inhibiting P-Glycoprotein ATPase
by I-Ting Wu, Chan-Yen Kuo, Ching-Hui Su, Yu-Hsuan Lan and Chin-Chuan Hung
Pharmaceuticals 2023, 16(2), 205; https://doi.org/10.3390/ph16020205 - 29 Jan 2023
Cited by 4 | Viewed by 1757
Abstract
Enhanced drug efflux through ATP-binding cassette transporters, particularly P-glycoprotein (P-gp), is a key mechanism underlying multidrug resistance (MDR). In the present study, we investigated the inhibitory effects of pinostrobin and tectochrysin on P-gp in MDR cancer cells and the underlying mechanisms. Fluorescence substrate [...] Read more.
Enhanced drug efflux through ATP-binding cassette transporters, particularly P-glycoprotein (P-gp), is a key mechanism underlying multidrug resistance (MDR). In the present study, we investigated the inhibitory effects of pinostrobin and tectochrysin on P-gp in MDR cancer cells and the underlying mechanisms. Fluorescence substrate efflux assays, multidrug resistance 1 (MDR1) shift assays, P-gp ATPase activity assays, Western blotting, and docking simulation were performed. The potential of the test compounds for MDR reversal and the associated molecular mechanisms were investigated through cell viability assay, cell cycle analysis, apoptosis assay, and further determining the combination index. Results demonstrated that pinostrobin and tectochrysin were not the substrates of P-gp, nor did they affect the expression of this transporter. Both compounds noncompetitively inhibited the efflux of rhodamine 123 and doxorubicin through P-gp. Furthermore, they resensitized MDR cancer cells to chemotherapeutic drugs, such as vincristine, paclitaxel, and docetaxel; thus, they exhibited strong MDR reversal effects. Our findings indicate that pinostrobin and tectochrysin are effective P-gp inhibitors and promising candidates for resensitizing MDR cancer cells. Full article
(This article belongs to the Special Issue Multidrug Resistance in Cancer: Pharmacological Strategies)
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15 pages, 3673 KiB  
Article
Long-Term Fenofibrate Treatment Stimulates the Phenotypic Microevolution of Prostate Cancer Cells In Vitro
by Karolina W. Warzecha, Maciej Pudełek, Jessica Catapano, Zbigniew Madeja and Jarosław Czyż
Pharmaceuticals 2022, 15(11), 1320; https://doi.org/10.3390/ph15111320 - 26 Oct 2022
Viewed by 1612
Abstract
Fenofibrate is a widely used anti-hyperlipidemic agonist of peroxisome proliferator-activated receptor alpha (PPARα). As a metabolic blocker, fenofibrate interferes with cancer promotion/progression via its misbalancing effects on cellular metabolism. However, the consequences of its long-term application for patients with diagnosed drug-resistant cancers are [...] Read more.
Fenofibrate is a widely used anti-hyperlipidemic agonist of peroxisome proliferator-activated receptor alpha (PPARα). As a metabolic blocker, fenofibrate interferes with cancer promotion/progression via its misbalancing effects on cellular metabolism. However, the consequences of its long-term application for patients with diagnosed drug-resistant cancers are unknown. We addressed this point by tracing the phenotypic microevolution of naïve and drug-resistant prostate cancer PC3_DCX20 cells that underwent a long-term exposition to 10 μM and 50 μM fenofibrate. Their resistance to fenofibrate, metabolic profile and invasive phenotype were estimated in the control conditions and under fenofibrate-induced stress. Apparently, drug efflux systems are not effective against the cytostatic FF action. However, wtPC3 and PC3_DCX20 cells that survived the long-term 50 μM fenofibrate treatment gave rise to lineages that displayed an increased proliferation rate, lower motility in the control conditions and enhanced fenofibrate resistance. Attenuated fenofibrate bioavailability modified the pattern of PC3 microevolution, as illustrated by phenotypic differences between wtPC3/PC3_DCX20 lineages propagated in the presence of 50 μM and 10 μM fenofibrate. Collectively, our observations indicate that fenofibrate acts as a selective factor that affects prostate cancer microevolution. We also pinpoint potential consequences of long-term exposition of prostate cancer patients to metabolic blockers. Full article
(This article belongs to the Special Issue Multidrug Resistance in Cancer: Pharmacological Strategies)
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