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Life Sci. 2005 Jun 3;77(3):252-65. Epub 2005 Feb 25.

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

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1
Graduate Institute of Medical Technology, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC.

Abstract

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 IIalpha 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 Bcl-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.

PMID:
15878354
DOI:
10.1016/j.lfs.2004.09.045
[Indexed for MEDLINE]
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