Ganoderic acid X, a lanostanoid triterpene, inhibits topoisomerases and induces apoptosis of cancer cells
Journal
Life Sciences
Journal Volume
77
Journal Issue
3
Pages
252-265
Date Issued
2005
Author(s)
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 IIα in vitro. Among the bioactive isolates, one of the most potent triterpene was identified to be 3α-hydroxy-15α-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. ? 2005 Elsevier Inc. All rights reserved.
SDGs
Other Subjects
3alpha hydroxy 15alpha acetoxylanosta 7,9(11),24 trien 26 oic acid; caspase 3; cytochrome c; DNA topoisomerase; DNA topoisomerase (ATP hydrolysing); ganoderma amboinense extract; mitogen activated protein kinase; plant extract; protein bcl xl; stress activated protein kinase; topoisomerase IIalpha; triterpene; unclassified drug; apoptosis; article; cancer cell culture; cancer inhibition; chromosome; controlled study; cytosol; DNA degradation; DNA synthesis inhibition; drug identification; drug isolation; drug potency; drug sensitization; enzyme activation; enzyme activity; enzyme inhibition; enzyme release; Ganoderma; ganoderma amboinense; hepatoma cell; human; human cell; medicinal plant; membrane damage; mitochondrial membrane; molecule; Antigens, Neoplasm; Antineoplastic Agents; Apoptosis; Caspase 3; Caspases; Cell Line, Tumor; Cell Proliferation; DNA Topoisomerases, Type I; DNA Topoisomerases, Type II, Eukaryotic; DNA-Binding Proteins; Enzyme Activation; Extracellular Signal-Regulated MAP Kinases; Ganoderma; Humans; JNK Mitogen-Activated Protein Kinases; Lanosterol; Medicine, Chinese Traditional; Molecular Structure; Neoplasms; Triterpenes; Ganoderma
Type
journal article