ijms-logo

Journal Browser

Journal Browser

Discovering Novel Bioactive Small Molecules against Drug-Resistant and Multidrug-Resistant Cancers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 1635

Special Issue Editor

Department of Physiology and Pharmacology, Chang Gung University, Tao-Yuan 333, Taiwan
Interests: multidrug resistance mechanisms; ATP-binding cassette proteins; protein kinase inhibitors; medicinal chemistry; natural products chemistry
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

A major obstacle to clinical cancer chemotherapy is the development of acquired drug-resistant or multidrug-resistance (MDR) phenotype in cancer cells. Multiple molecular mechanisms such as increased drug efflux, reduced drug uptake, enhanced cellular repair mechanisms, and alterations of drug metabolism or drug targets are known to contribute to the reduced sensitivity of cancer cells to anticancer drugs. In the past decade, many synthetic compounds have been developed; natural bioactive compounds have been discovered, and numerous therapeutic agents have been repurposed to improve the efficacy of anticancer drugs in these drug-resistant cancer cells. This Special Issue on “Discovering novel bioactive small molecules against drug-resistant and multidrug-resistant cancers” warmly invites researchers to contribute original research articles, review articles, and short communications related to all aspects of drug development and therapeutic approaches against drug-resistant and multidrug-resistant cancers.

Prof. Dr. Chung-Pu Wu
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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.

Published Papers (1 paper)

Order results
Result details
Select all
Export citation of selected articles as:

Research

20 pages, 6468 KiB  
Article
Hydroxygenkwanin Improves the Efficacy of Cytotoxic Drugs in ABCG2-Overexpressing Multidrug-Resistant Cancer Cells
by Yan-Qing Li, Megumi Murakami, Yang-Hui Huang, Tai-Ho Hung, Shun-Ping Wang, Yu-Shan Wu, Suresh V. Ambudkar and Chung-Pu Wu
Int. J. Mol. Sci. 2022, 23(21), 12763; https://doi.org/10.3390/ijms232112763 - 23 Oct 2022
Viewed by 1396
Abstract
Hydroxygenkwanin, a flavonoid isolated from the leaves of the Daphne genkwa plant, is known to have pharmacological properties; however, its modulatory effect on multidrug resistance, which is (MDR) mediated by ATP-binding cassette (ABC) drug transporters, has not been investigated. In this study, we [...] Read more.
Hydroxygenkwanin, a flavonoid isolated from the leaves of the Daphne genkwa plant, is known to have pharmacological properties; however, its modulatory effect on multidrug resistance, which is (MDR) mediated by ATP-binding cassette (ABC) drug transporters, has not been investigated. In this study, we examine the interaction between hydroxygenkwanin, ABCB1, and ABCG2, which are two of the most well-characterized ABC transporters known to contribute to clinical MDR in cancer patients. Hydroxygenkwanin is not an efflux substrate of either ABCB1 or ABCG2. We discovered that, in a concentration-dependent manner, hydroxygenkwanin significantly reverses ABCG2-mediated resistance to multiple cytotoxic anticancer drugs in ABCG2-overexpressing multidrug-resistant cancer cells. Although it inhibited the drug transport function of ABCG2, it had no significant effect on the protein expression of this transporter in cancer cells. Experimental data showing that hydroxygenkwanin stimulates the ATPase activity of ABCG2, and in silico docking analysis of hydroxygenkwanin binding to the inward-open conformation of human ABCG2, further indicate that hydroxygenkwanin sensitizes ABCG2-overexpressing cancer cells by binding to the substrate-binding pocket of ABCG2 and attenuating the transport function of ABCG2. This study demonstrates the potential use of hydroxygenkwanin as an effective inhibitor of ABCG2 in drug combination therapy trials for patients with tumors expressing higher levels of ABCG2. Full article
Show Figures

Figure 1

Back to TopTop