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Title: Effect of thai plant extracts on p-glycoprotein function and viability in paclitaxel-resistant HepG2 cells
Authors: Masashi Kawami
Ryoko Yumoto
Junya Nagai
Varaporn Buraphacheep Junyaprasert
Noppamas Soonthornchareonnon
Denpong Patanasethanont
Bung Orn Sripanidkulchai
Takano Mikihisa
Hiroshima University
Mahidol University
Khon Kaen University
Keywords: Medicine;Pharmacology, Toxicology and Pharmaceutics
Issue Date: 1-Jan-2010
Citation: Drug Metabolism and Pharmacokinetics. Vol.25, No.2 (2010), 155-162
Abstract: The effects of ethanol extracts from Thai plants on P-glycoprotein (P-gp) function and cell viability were examined using paclitaxel-resistant HepG2 (PR-HepG2) cells. KP018 from Ellipeiopsis cherrevensis and AT80 from Ancistrocladus tectorius increased both rhodamine 123, a typical P-gp substrate, and [3H]paclitaxel uptake in PR-HepG2 cells. However, some extracts such as MT80 from Microcos tomentosa increased rhodamine 123, but not [3H]paclitaxel, uptake, while MM80 from Micromelum minutum increased only [3H]paclitaxel uptake. Thus, the effects of extracts of Thai plants on rhodamine 123 uptake were not necessarily the same as those on [3H]paclitaxel uptake. Purified compounds such as bergapten did not affect the uptake of either substrate. KP018, AT80, and MM80 increased [3H]paclitaxel uptake and decreased the cell viability in a concentration-dependent manner. Among these extracts, KP018 showed the most potent cytotoxicity. The cytotoxic potency of KP018 on PR-HepG2 cells was similar to that on wild-type HepG2 cells, and was not potentiated by verapamil. At concentrations resulting in no cytotoxicity, AT80 and MM80 potentiated paclitaxel-induced cytotoxicity in PR-HepG2 cells. These results indicate that K018 may be a useful source to search for a new anticancer drug, while AT80 and MM80 may be useful as modulators of P-gp-mediated multidrug resistance in cancer cells.
ISSN: 18800920
Appears in Collections:Scopus 2006-2010

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