Effect of Thai Plant Extracts on P-glycoprotein Function and Viability in Paclitaxel-Resistant HepG2 Cells

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  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.<br>

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