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Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Polyphenols Counteract Tumor Cell Chemoresistance Conferred by Multidrug Resistance Proteins

Author(s): Krystyna Michalak and Olga Wesolowska

Volume 12, Issue 8, 2012

Page: [880 - 890] Pages: 11

DOI: 10.2174/187152012802650011

Price: $65

Abstract

One of the main reasons of cancer resistance to chemotherapeutic treatment is the presence of different ABC multidrug transporters in plasma membranes. The transporters extrude wide spectrum of anticancer agents out of cancer cells at the expense of energy derived from ATP-hydrolysis. Plant-origin polyphenolic compounds, mainly flavonoids and stilbenes or their synthetic derivatives, can modulate the main ABC transporters responsible for cancer drug resistance, including P-glycoprotein, MRP1 and BCRP. The recent studies on different resistant cancer cell lines enabled the discovery of a number of polyphenolic compounds able to reverse drug resistance in vitro and these compounds could be promising candidates for further clinical trials. The review summarizes the recent advances in the field of polyphenols interaction with ATP-binding cassette multidrug transporters. The mechanism of flavonoids interactions with the multidrug transporters and the structure-activity relationship are also discussed.

Keywords: ABC transporters, Breast cancer resistance protein (BCRP), Flavonoids, Multidrug resistance (MDR), MDR modulators, MDR reversal, Multidrug resistance-associated protein 1 (MRP1), P-glycoprotein (P-gp), Polyphenols, Stilbenes


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