Abstract
Asiatic acid (AA), a triterpene, is known to be cytotoxic to several tumor cell lines. AA induces dose- and time-dependent cell death in U-87 MG human glioblastoma. This cell death occurs via both apoptosis and necrosis. The effect of AA may be cell type-specific as AA-induced cell death was mainly apoptotic in colon cancer RKO cells. AA-induced glioblastoma cell death is associated with decreased mitochondrial membrane potential, activation of caspase-9 and -3, and increased intracellular free Ca2+. Although treatment of glioblastoma cells with the caspase inhibitor zVAD-fmk completely abolished AA-induced caspase activation, it did not significantly block AA-induced cell death. AA-induced cell death was significantly prevented by an intracellular Ca2+ inhibitor, BAPTA/AM. Taken together, these results indicate that AA induces cell death by both apoptosis and necrosis, with Ca2+-mediated necrotic cell death predominating.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Chloromethyl Ketones / pharmacology
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Antineoplastic Agents / pharmacology*
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Apoptosis / drug effects*
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Calcium / metabolism
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Caspase 3 / biosynthesis
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Caspase 9 / biosynthesis
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Caspase Inhibitors
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Cell Line, Tumor
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Cell Survival / drug effects
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Chelating Agents / pharmacology
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Colonic Neoplasms / drug therapy
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Colonic Neoplasms / metabolism
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Colonic Neoplasms / pathology
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Cysteine Proteinase Inhibitors / pharmacology
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DNA Fragmentation
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Dose-Response Relationship, Drug
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Drug Screening Assays, Antitumor
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Egtazic Acid / analogs & derivatives
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Egtazic Acid / pharmacology
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Glioblastoma / drug therapy*
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Glioblastoma / metabolism
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Glioblastoma / pathology
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Humans
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Membrane Potential, Mitochondrial / drug effects
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Necrosis / chemically induced*
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Pentacyclic Triterpenes
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Triterpenes / pharmacology*
Substances
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Amino Acid Chloromethyl Ketones
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Antineoplastic Agents
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Caspase Inhibitors
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Chelating Agents
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Cysteine Proteinase Inhibitors
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Pentacyclic Triterpenes
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Triterpenes
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benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
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1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester
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Egtazic Acid
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asiatic acid
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Caspase 3
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Caspase 9
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Calcium