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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.

Synaptic vesicles are among the best characterized membranous organelles. A rat pheochromocytoma cell line, PC12, makes vesicles of the same size, density and membrane composition as authentic synaptic vesicles, isolated from rat brain (Clift-O’Grady et al., 1990). These organelles have been termed “synaptic vesicle-like vesicles” (SVLVs). In recent years PC12 cells have been used by several investigators as a model system for studying synaptic vesicle biogenesis and the targeting of synaptic vesicle-specific proteins. Evidence has accumulated from these studies that synaptic vesicles can be derived by endocytosis and that the precursor organelle in the nerve terminal is either the plasma membrane or an early endosomal compartment (Johnston et al., 1989; Clift-O’Grady et al., 1990; Regnier-Vigouroux et al., 1991).