Effect of Thai plant extracts on P-glycoprotein function and viability in paclitaxel-resistant HepG2 cells.
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 [(3)H]paclitaxel uptake in PR-HepG2 cells. However, some extracts such as MT80 from Microcos tomentosa increased rhodamine 123, but not [(3)H]paclitaxel, uptake, while MM80 from Micromelum minutum increased only [(3)H]paclitaxel uptake. Thus, the effects of extracts of Thai plants on rhodamine 123 uptake were not necessarily the same as those on [(3)H]paclitaxel uptake. Purified compounds such as bergapten did not affect the uptake of either substrate. KP018, AT80, and MM80 increased [(3)H]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.
Kawami
Masashi
M
Department of Pharmaceutics and Therapeutics, Hiroshima University, Japan.
Yumoto
Ryoko
R
Nagai
Junya
J
Junyaprasert
Varaporn Buraphacheep
VB
Soonthornchareonnon
Noppamas
N
Patanasethanont
Denpong
D
Sripanidkulchai
Bung-orn
BO
Takano
Mikihisa
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects* / Q000493:pharmacokinetics; D029061:Annonaceae / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects* / Q000502:physiology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004357:Drug Synergism; D056945:Hep G2 Cells / Q000187:drug effects / Q000502:physiology; D029001:Herbal Medicine / Q000379:methods; D006801:Humans; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism*; D017239:Paclitaxel / Q000493:pharmacokinetics*; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D020112:Rhodamine 123 / Q000493:pharmacokinetics*; D027821:Rutaceae / Q000737:chemistry*; D013785:Thailand; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000493:pharmacokinetics
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D017239:Paclitaxel; D010936:Plant Extracts; D020112:Rhodamine 123; D014700:Verapamil