Modulation of P-glycoprotein function and multidrug resistance in cancer cells by Thai plant extracts
Modulation of P-glycoprotein function and multidrug resistance in cancer cells by Thai plant extracts
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DOI：
10.1691/ph.2014.4619
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发表时间：
2014-11-01
期刊：
影响因子：
1.6
通讯作者：
Yumoto, R.
中科院分区：
文献类型：
--
作者：
Takano, M.;Kakizoe, S.;Yumoto, R.
研究了泰国番荔枝科、芸香科和姜科植物乙醇提取物对紫杉醇抗性HepG2 （PR-HepG2）细胞p -糖蛋白（P-gp）功能和多药耐药性的影响。所有被测的提取物都显著增加了P-gp底物[H-3]紫杉醇在细胞中的积累。在9种提取物中，莪术提取物Z01和姜科山柰提取物Z02均能显著提高其积累量。此外，Z01和Z02以浓度依赖性的方式增加了PR-HepG2细胞中其他P-gp底物罗丹明123和阿霉素的积累。激光共聚焦扫描显微镜也证实了Z01和Z02对罗丹明123和阿霉素的积累增加。同时检测Z01和Z02预处理对MDR1 mRNA表达的影响。用这些提取物处理PR-HepG2细胞48小时后，MDR1 mRNA的表达不受影响。用XTT法和蛋白法检测了Z02存在和不存在情况下紫杉醇的细胞毒性。Z02增强紫杉醇对PR-HepG2细胞的细胞毒性。这些结果表明，姜科姜黄和山柰是寻找新的P-gp调节剂以克服癌细胞多药耐药的有益来源。
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 [H-3]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.