Ganoderic acid X, a lanostanoid triterpene, inhibits topoisomerases and induces apoptosis of cancer cells

LIFE SCIENCES

卷:77

Article

Li, CH ; Chen, PY ; Chang, UM ; Kan, LS ; Fang, WH ; Tsai, KS ; Lin, SB

关键词: Ganoderma triterpene;    ganoderic acid X;    apoptosis;    topoisomerase inhibitor;   

DOI  :  10.1016/j.lfs.2004.09.045

来源: Elsevier

【 摘 要 】

Lanostanoid triterpenes isolated from Ganoderma amboinense were found to inhibit the growth of numerous cancer cell lines, and some of them inhibited the activities of topoisomerases I and II alpha in vitro. Among the bioactive isolates, one of the most potent triterpene was identified to be 3 alpha-hydroxy-15 alpha-acetoxy-lanosta-7,9(11),24-trien-26-oic acid, ganoderic acid X (GAX). Treatment of human hepatoma HuH-7 cells with GAX caused immediate inhibition of DNA synthesis as well as activation of ERK and JNK mitogen-activated protein kinases, and cell apoptosis. Molecular events of apoptosis including degradation of chromosomal DNA, decrease in the level of Bc1-xL, the disruption of mitochondrial membrane, cytosolic release of cytochrome c and activation of caspase-3 were elucidated. The ability of GAX to inhibit topoisomerases and to sensitize the cancer cells toward apoptosis fulfills the feature of a potential anticancer drug. (c) 2005 Elsevier Inc. All rights reserved.

【 授权许可】

Free