期刊
PROCESS BIOCHEMISTRY
卷 46, 期 6, 页码 1307-1314出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.procbio.2011.02.023
关键词
Ganoderic acid Me; Multidrug resistance; MDR1; MRPs; Apoptosis
资金
- National Special Fund for State Key Laboratory of Bioreactor Engineering [2060204]
- modernization of Chinese medicine special project for Shanghai Technology Innovation Action Plan [08DZ1971900]
- 111 Project [B07023]
- Shanghai Science and Technology Commission [054319933]
Ganoderma lucidum is known as a valuable herb in the search for anticancer lead compounds because it has been used for thousands of years as a traditional medication. Triterpenoids are the principal active components in this fungus. Ganoderic acid Me (GA-Me), a pure lanostane triterpene, was isolated from G. lucidum. Our study showed that GA-Me could reverse the multidrug resistance (MDR) in multidrug resistant clone cancer cells. We investigated that GA-Me enhanced the chemosensitivities of anticancer agents in MDR cells. Furthermore. GA-Me inhibited the activity of hMDR1 promoter and this transcriptional suppression was consistent with the inhibitory effect of GA-Me on the mRNA and protein expression level of MDR1. Meanwhile, the expression levels of MRP1 and MRP2 were also inhibited by GA-Me. GA-Me could induce apoptosis in MDR cells via up-regulation of p-p53, p53, Bax, caspase-3, caspase-9 and down-regulation of Bcl-2. In addition, GA-Me stimulated the decline in mitochondrial membrane potential and cytochrome release into cytosol. We concluded that GA-Me could effectively reverse multidrug resistance in MDR colon cancer cells, via repressing expression levels of MDR1, MRPs and regulating apoptosis-related pathways. These results suggested that GA-Me had therapeutic potential against multiclrug resistance as a new agent. (C) 2011 Elsevier Ltd. All rights reserved.
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