Enhanced sensitivity of A549 cells to the cytotoxic action of anticancer drugs via suppression of Nrf2 by procyanidins from Cinnamomi Cortex extract

被引:52
|
作者
Ohnuma, Tomokazu [1 ]
Matsumoto, Takashi [1 ]
Itoi, Ayano [1 ]
Kawana, Ayako [1 ]
Nishiyama, Takahito [1 ]
Ogura, Kenichiro [1 ]
Hiratsuka, Akira [1 ]
机构
[1] Tokyo Univ Pharm & Life Sci, Sch Pharm, Dept Drug Metab & Mol Toxicol, Hachioji, Tokyo 1920392, Japan
关键词
Nrf2; Lung cancer; Cinnamomi Cortex; Sensitivity; Anticancer drugs; Procyanidin; LUNG-CANCER; RESISTANCE; EXPRESSION; PROTEINS; GROWTH; KEAP1; CHROMATOGRAPHY; OLIGOMERS; PATHWAY; ENZYMES;
D O I
10.1016/j.bbrc.2011.09.014
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Nuclear factor-E2-related factor 2 (Nrf2) is an important cytoprotective transcription factor because Nrf2-regulated enzymes play a key role in antioxidant and detoxification processes. Recent studies have reported that lung cancer cells overexpressing Nrf2 exhibit increased resistance to chemotherapy. Suppression of overexpressed Nrf2 is needed for a new therapeutic approach against lung cancers. In the present study, we found that Cinnamomi Cortex extract (CCE) has an ability to suppress Nrf2-regulated enzyme activity and Nrf2 expression in human lung cancer A549 cells with high Nrf2 activity. Moreover, we demonstrated that CCE significantly enhances sensitivity of A549 cells to the cytotoxic action of doxorubicin and etoposide as well as increasing the intracellular accumulation of both drugs. These results suggest that CCE might be an effective concomitant agent to reduce anticancer drug resistance derived from Nrf2 overexpression. Bioactivity-guided fractionation revealed that procyanidin tetramers and pentamers contained in CCE were active components in suppressing Nrf2. (C) 2011 Elsevier Inc. All rights reserved.
引用
收藏
页码:623 / 629
页数:7
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