benzyloxycarbonylvalyl-alanyl-aspartyl-fluoromethyl-ketone and asiatic-acid

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.

Topics: Amino Acid Chloromethyl Ketones; Antineoplastic Agents; Apoptosis; Calcium; Caspase 3; Caspase 9; Caspase Inhibitors; Cell Line, Tumor; Cell Survival; Chelating Agents; Colonic Neoplasms; Cysteine Proteinase Inhibitors; DNA Fragmentation; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Egtazic Acid; Glioblastoma; Humans; Membrane Potential, Mitochondrial; Necrosis; Pentacyclic Triterpenes; Triterpenes