Abstract
Multidrug resistance is a phenomenon whereby tumors become resistant to structurally unrelated anticancer drugs. P-glycoprotein belongs to the large ATP-binding cassette (ABC) transporter superfamily of membrane transport proteins. P-glycoprotein mediates resistance to various classes of anticancer drugs including vinblastine, daunorubicin, and paclitaxel, by actively extruding the drugs from the cells. The quest for inhibitors of anticancer drug efflux transporters has uncovered natural compounds, including (-)-epigallocatechin gallate, curcumin, capsaicin, and guggulsterone, as promising candidates. In this review, studies on the effects of natural compounds on P-glycoprotein and anticancer drug efflux transporters are summarized.
Highlights
Cancer is the leading cause of death in Japan, and the second cause of death in the United States.Carcinogenesis is generally recognized as a multistep process in which a normal cell acquires specific phenotypic characteristics including self-sufficiency in growth signals, evasion of apoptosis, limitless replicative potential, sustained angiogenesis and the ability to undergo tissue invasion and metastasis [1].Cancer chemotherapy is the treatment of cancer using anticancer drugs with the aim to achieve and maintain remission
In addition to the anti-carcinogenic effects of Epigallocatechin gallate (EGCG), we have revealed the inhibitory effects of EGCG and other tea catechins on the function of P-glycoprotein using human carcinoma KB-C2 cells and fluorescent P-glycoprotein substrates daunorubicin and rhodamine 123 [10]
We have examined the inhibitory effect of curcumin on human P-glycoprotein using
Summary
Cancer is the leading cause of death in Japan, and the second cause of death in the United States. (-)-Epigallocatechin gallate, curcumin, and capsaicin serve as a wide variety of naturally occurring phytochemicals with cancer chemopreventive activity [5,6,7]. Several studies have documented the ability of chemopreventive phytochemicals to increase the sensitivity of cancer cells to anticancer drugs. Natural compounds including flavonoids such as quercetin, morin, and (-)-epigallocatechin gallate, curcumin, capsaicin, and [6]-gingerol can reverse the multidrug resistance by the inhibition of anticancer drug efflux transporter P-glycoprotein and other ABC transporters [8,9,10,11]. Studies on the effects of natural compounds on ABC transporters are summarized, for the future development of safe and effective inhibitors of ABC transporters to overcome multidrug resistance in human cancer
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