Modulation of P-glycoprotein function and multidrug resistance in cancer cells by Thai plant extracts

The effects of ethanol extracts from Thai plants belonging to the families of Annonaceae, Rutaceae, and Zingiberaceae on P-glycoprotein (P-gp) function and multidrug resistance were examined in paclitaxel-resistant HepG2 (PR-HepG2) cells. All the extracts tested, significantly increased the accumula...

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Veröffentlicht in:Pharmazie 2014-11, Vol.69 (11), p.823-828
Hauptverfasser: Takano, M, Kakizoe, S, Kawami, M, Nagai, J, Patanasethnont, D, Sripanidkulchai, B, Yumoto, R
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container_end_page 828
container_issue 11
container_start_page 823
container_title Pharmazie
container_volume 69
creator Takano, M
Kakizoe, S
Kawami, M
Nagai, J
Patanasethnont, D
Sripanidkulchai, B
Yumoto, R
description The effects of ethanol extracts from Thai plants belonging to the families of Annonaceae, Rutaceae, and Zingiberaceae on P-glycoprotein (P-gp) function and multidrug resistance were examined in paclitaxel-resistant HepG2 (PR-HepG2) cells. All the extracts tested, significantly increased the accumulation of [3H]paclitaxel, a P-gp substrate, in the cells. Among nine extracts, Z01 and Z02, extracts from Curcuma comosa and Kaempferia marginata (Zingiberaceae family), respectively, potently increased the accumulation. In addition, Z01 and Z02 increased the accumulation of other P-gp substrates, rhodamine 123 and doxorubicin, in PR-HepG2 cells in a concentration-dependent manner. Increased accumulation of rhodamine 123 and doxorubicin by Z01 and Z02 was also confirmed by confocal laser scanning microscopy. The effect of Z01 and Z02 pretreatment on the expression of MDR1 mRNA was also examined. The expression of MDR1 mRNA was not affected by the treatment of PR-HepG2 cells with these extracts for 48 hours. Cytotoxicity of paclitaxel was examined by XTT and protein assays in the absence and presence of Z02. Z02 potentiated the cytotoxicity of paclitaxel in PR-HepG2 cells. These results suggest that Curcuma comosa and Kaempferia marginata belonging to Zingiberaceae are useful sources to search for new P-gp modulator(s) that can be used to overcome multidrug resistance of cancer cells.
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subjects Antibiotics, Antineoplastic - metabolism
Antineoplastic Agents, Phytogenic - pharmacology
ATP Binding Cassette Transporter, Sub-Family B - biosynthesis
ATP Binding Cassette Transporter, Sub-Family B - genetics
ATP-Binding Cassette, Sub-Family B, Member 1 - drug effects
ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism
Cell Line, Tumor
Doxorubicin - metabolism
Drug Resistance, Multiple - drug effects
Drug Resistance, Neoplasm - drug effects
Hep G2 Cells
Humans
Paclitaxel - metabolism
Paclitaxel - pharmacology
Plant Extracts - pharmacology
Plants, Medicinal - chemistry
Thailand
title Modulation of P-glycoprotein function and multidrug resistance in cancer cells by Thai plant extracts
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