Abstract
Because betulinic acid was recently described as a melanoma-specific inducer of apoptosis, we investigated whether this agent was comparably effective against metastatic tumors and those in which metastatic ability and 92-kD gelatinase activity had been decreased by introduction of a normal chromosome 6. Human metastatic C8161 melanoma cells showed greater DNA fragmentation and growth arrest and earlier loss of viability in response to betulinic acid than their non-metastatic C8161/neo 6.3 counterpart. These effects involved induction of p53 without activation of p21WAF1 and were synergized by bromodeoxyuridine in metastatic Mel Juso, with no comparable responses in non-metastatic Mel Juso/neo 6 cells. Our data suggest that betulinic acid exerts its inhibitory effect partly by increasing p53 without a comparable effect on p21WAF1.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents, Phytogenic / pharmacology*
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Betulinic Acid
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Cell Death / drug effects
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Cell Death / genetics
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Cyclin D1 / metabolism
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Cyclin D3
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins / biosynthesis
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Cyclins / metabolism*
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DNA Damage
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Drug Resistance, Neoplasm
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Gelatinases / metabolism
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Gene Expression Regulation, Neoplastic / drug effects*
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Humans
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Melanoma / drug therapy
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Melanoma / enzymology
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Melanoma / genetics
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Melanoma / metabolism*
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Neoplasm Metastasis
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Pentacyclic Triterpenes
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Triterpenes / pharmacology*
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Tumor Cells, Cultured
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Tumor Suppressor Protein p53 / biosynthesis*
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Tumor Suppressor Protein p53 / genetics
Substances
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Antineoplastic Agents, Phytogenic
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CCND3 protein, human
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CDKN1A protein, human
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Cyclin D3
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins
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Pentacyclic Triterpenes
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Triterpenes
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Tumor Suppressor Protein p53
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Cyclin D1
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Gelatinases
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Betulinic Acid