1. Glioblastoma cell death induced by asiatic acid
- Author
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M. H. Cardone, Chan-Wha Kim, D. S. Choi, Anthony J. Sinskey, C. W. Cho, and Chokyun Rha
- Subjects
Programmed cell death ,Necrosis ,Cell Survival ,Health, Toxicology and Mutagenesis ,Cell ,Antineoplastic Agents ,Apoptosis ,DNA Fragmentation ,Cysteine Proteinase Inhibitors ,Biology ,Toxicology ,Amino Acid Chloromethyl Ketones ,chemistry.chemical_compound ,BAPTA ,Cell Line, Tumor ,medicine ,Humans ,Cytotoxic T cell ,Egtazic Acid ,Chelating Agents ,Membrane Potential, Mitochondrial ,Dose-Response Relationship, Drug ,Caspase 3 ,Cell Biology ,Caspase Inhibitors ,Caspase 9 ,Triterpenes ,Cell biology ,medicine.anatomical_structure ,chemistry ,Cell culture ,Colonic Neoplasms ,Cancer research ,Calcium ,Drug Screening Assays, Antitumor ,medicine.symptom ,Glioblastoma ,Pentacyclic Triterpenes ,Intracellular - 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.
- Published
- 2006
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