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Transporter-Mediated Multidrug Resistance and its Modulation by Chinese Medicines and Other Herbal Products

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Abstract:

The main cause of failure in cancer drug therapy is the emergence of cellular resistance to drugs. Cancer cells, after exposure to one drug, can become simultaneously insensitive to mechanistically and chemically unrelated drugs, a phenotype known as multidrug resistance (MDR). Although a number of mechanisms have been proposed to mediate MDR, the classical cellular mechanism involves the overexpression of several members of the ATP-binding cassette (ABC) superfamily of transporters, leading to increased efflux and decreased intracellular drug accumulation. Among these, P-glycoprotein (P-gp, ABCB1), MRP1 (ABCC1) and BCRP (ABCG2) are the main transporters conferring MDR. These transporters are frequently detected in recurrent cancer cells or cancer stem cells. To overcome MDR, various studies have been conducted to investigate the potential to discover effective MDR modulators from Chinese medicines (CMs) and other herbal products because many of these have been used for centuries without harmful side effects. This review summarizes: i) The contribution of P-gp, MRP1 and BCRP in cancer drug resistance; ii) known mechanisms of action for MDR modulators; iii) commonly used methods for identification and evaluation of novel modulators of transporter- mediated MDR; and iv) the modulating effects of CMs and other natural products on ABC transporters and MDR. The CM and their active components with potent modulating effects on MDR can be considered as promising lead agents for the design of more effective and less toxic drugs to overcome MDR.





Keywords: Chinese Medicines; MDR modulators; multidrug resistance; transporters

Document Type: Research Article

Publication date: March 1, 2010

More about this publication?
  • Due to the plethora of new approaches being used in modern drug discovery by the pharmaceutical industry, Current Drug Discovery Technologies has been established to provide comprehensive overviews of all the major modern techniques and technologies used in drug design and discovery. The journal is the forum for publishing both original research papers and reviews describing novel approaches and cutting edge technologies used in all stages of drug discovery. The journal addresses the multidimensional challenges of drug discovery science including integration issues of the drug discovery process.

    Current Drug Discovery Technologies is an essential journal for all scientists and research managers involved in drug discovery who wish to keep abreast of all the modern techniques and technologies used in drug discovery.
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