Glioblastoma cell death induced by asiatic acid |
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| Authors: | C W Cho D S Choi M H Cardone C W Kim A J Sinskey C Rha |
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| Institution: | (1) Biomaterials Science and Engineering Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA;(2) School of Life Sciences and Biotechnology, Korea University, Seoul, South Korea;(3) Eutropics Pharmaceuticals Inc., Dorchester, Massachusetts, USA;(4) Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA;(5) Biomaterials Science and Engineering Laboratory, Massachusetts Institute of Technology, 56–265, 77 Massachusetts Avenue, Cambridge, MA 02139, USA |
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| 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. |
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| Keywords: | asiatic acid triterpene glioblastoma apoptosis necrosis caspase-independent death |
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