Effects of Ganoderic acid Me on inhibiting multidrug resistance and inducing apoptosis in multidrug resistant colon cancer cells

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• 作者：Zijing Jiang^a ; Tiantian Jin^a ; Feng Gao^a ; Jianwen Liu^a ; ^{liujian@ecust.edu.cn"" rel=""nofollow} ; Jianjiang Zhong^b ; ^{jjzhong@sjtu.edu.cn"" rel=""nofollow} ; Heng Zhao^c ; ^{h_zhao28@163.com"" rel=""nofollow}
• 关键词：Ganoderic acid Me ; Multidrug resistance ; MDR1 ; MRPs ; Apoptosis
• 刊名：Process Biochemistry
• 出版年：2011
• 出版时间：June 2011
• 年：2011
• 卷：46
• 期：6
• 页码：1307-1314
• 全文大小：1294 K

文摘

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 multidrug resistance as a new agent.