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

被引：121

作者：

Li, CH

Chen, PY

Chang, UM

Kan, LS

Fang, WH

Tsai, KS

Lin, SB

机构：

[1] Natl Taiwan Univ, Coll Med, Grad Inst Med Technol, Taipei, Taiwan

[2] Natl Taiwan Univ Hosp, Dept Lab Med, Taipei, Taiwan

[3] Acad Sinica, Inst Chem, Taipei, Taiwan

来源：

LIFE SCIENCES | 2005年 / 77卷 / 03期

关键词：

Ganoderma triterpene; ganoderic acid X; apoptosis; topoisomerase inhibitor;

D O I：

10.1016/j.lfs.2004.09.045

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

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.

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页码：252 / 265

页数：14

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