Modulation of function of multidrug resistance associated-proteins by Kaempferia parviflora extracts and their components
Modulation of function of multidrug resistance associated-proteins by Kaempferia parviflora extracts and their components
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DOI：
10.1016/j.ejphar.2007.04.001
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发表时间：
2007-07-02
影响因子：
5
通讯作者：
Takano, Mikihisa
中科院分区：
文献类型：
--
作者：
Patanasethanont, Denpong;Nagai, Junya;Takano, Mikihisa
本研究以A549细胞为研究对象，研究了山茶根茎提取物和黄酮衍生物对A549细胞多药耐药相关蛋白(MRP)转运的影响。细胞表达MRP1和MRP2，但不表达P-糖蛋白。不同的MRP抑制剂可显著增加MRP底物钙黄素的细胞积累量，而不受典型的P-糖蛋白抑制剂维拉帕米的影响。小花根茎乙醇和水提物可浓度依赖地增加钙黄绿素和阿霉素在A549细胞中的积累量。乙醇提取物对MRP功能的抑制作用强于水提物。在6种黄酮衍生物中，5，7-二甲氧基黄酮类化合物对阿霉素在A549细胞中的积累有最大的促进作用。4个不含5-羟基的黄酮衍生物对阿霉素的累积有促进作用，而另外两个不含5-羟基的黄酮衍生物对阿霉素的累积无明显影响。此外，5，7-二甲氧基黄酮和3，5，7，3‘，4’-五甲氧基黄酮降低了A549细胞对阿霉素的耐药性。这些发现表明，小花红景天的提取物和黄酮衍生物抑制MRP功能，因此可能是癌细胞多药耐药的调节剂。(C)2007 Elsevier B.V.保留所有权利。
In this study, the effects of extracts and flavone derivatives from the rhizome of Kaempferia parviflora on multidrug resistance associated-proteins (MRP)-mediated transport in A549 cells were examined. The cells employed express MRP1 and MRP2, but not P-glycoprotein. The cellular accumulation of calcein, an MRP substrate, was significantly increased by various MRP inhibitors without being affected by verapamil, a typical P-glycoprotein inhibitor. Ethanol and aqueous extracts from K parviflora rhizome increased the accumulation of calcein and doxorubicin in A549 cells in a concentration-dependent manner. The inhibitory potency of the ethanol extract for MRP function was greater than that of the aqueous extract. Among six flavone derivatives isolated from K. parviflora rhizome, 5,7-dimethoxyflavone exhibited a maximal stimulatory effect on the accumulation of doxorubicin in A549 cells. The accumulation of doxorubicin was increased by four flavone derivatives without 5-hydroxy group, but not by the other two flavone derivatives with 5-hydroxy group. In addition, 5,7-dimethoxyflavone and 3,5,7,3',4'-pentamethoxyflavone decreased resistance to doxorubicin in A549 cells. These findings indicate that extracts and flavone derivatives from the rhizome of K. parviflora suppress MRP function, and therefore may be useful as modulators of multidrug resistance in cancer cells. (c) 2007 Elsevier B.V. All rights reserved.