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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, Neoplasm / metabolism
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Antineoplastic Agents* / chemistry
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Antineoplastic Agents* / metabolism
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Apoptosis / physiology*
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Caspase 3
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Caspases / metabolism
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Cell Line, Tumor
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Cell Proliferation
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DNA Topoisomerases, Type I / metabolism
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DNA Topoisomerases, Type II / metabolism
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DNA-Binding Proteins / antagonists & inhibitors*
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DNA-Binding Proteins / metabolism
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Enzyme Activation
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Ganoderma / chemistry
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Humans
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JNK Mitogen-Activated Protein Kinases / metabolism
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Lanosterol* / analogs & derivatives*
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Lanosterol* / chemistry
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Lanosterol* / metabolism*
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Lanosterol* / therapeutic use
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Medicine, Chinese Traditional
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Molecular Structure
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Neoplasms / drug therapy
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Neoplasms / metabolism
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Topoisomerase I Inhibitors*
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Topoisomerase II Inhibitors*
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Triterpenes* / chemistry
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Triterpenes* / metabolism*
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Triterpenes* / therapeutic use
Substances
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3alpha-hydroxy-15alpha-acetoxy-lanosta-7,9(11),24-trien-26-oic acid
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Antigens, Neoplasm
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Antineoplastic Agents
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DNA-Binding Proteins
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Topoisomerase I Inhibitors
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Topoisomerase II Inhibitors
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Triterpenes
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Lanosterol
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Extracellular Signal-Regulated MAP Kinases
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JNK Mitogen-Activated Protein Kinases
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CASP3 protein, human
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Caspase 3
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Caspases
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DNA Topoisomerases, Type I
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DNA Topoisomerases, Type II