Discovering natural product modulators to overcome multidrug resistance in cancer chemotherapy.
Multidrug resistance caused by the overexpression of ABC drug transporters is a major obstacle in clinical cancer chemotherapy. For several years, it appeared that direct inhibition of ABC transporters would be the cheapest and most efficient way to combat this problem. Unfortunately, progress in finding a potent, selective inhibitor to modulate ABC transporters and restore drug sensitivity in multidrug-resistant cancer cells has been slow and challenging. Candidate drugs should ideally be selective, potent and relatively non-toxic. Many researchers in recent years have turned their attention to utilizing natural products as the building blocks for the development of the next generation of inhibitors, especially after the disappointing results obtained from inhibitors of the first three generations at the clinical trial stage. The first step is to discover natural substances (distinct from the first three generation inhibitors) that are potent, selective and relatively non-toxic in order to be used clinically. Here, we present a brief overview of the prospect of using natural products to modulate the function of ABC drug transporters clinically and their impact on human physiology and pharmacology.
Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Chung-Pu
CP
Wu
Shinobu
S
Ohnuma
Suresh V
SV
Ambudkar
D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors* / Q000235:genetics; D000818:Animals; D001688:Biological Products / Q000302:isolation & purification / Q000627:therapeutic use*; D055808:Drug Discovery; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism
D018528:ATP-Binding Cassette Transporters; D001688:Biological Products