Related Experiment Video
Updated: Aug 2, 2026
Isolation and Flow Cytometric Analysis of Glioma-infiltrating Peripheral Blood Mononuclear Cells
Published on: November 28, 2015
Glioblastoma cell death induced by asiatic acid
C W Cho1, D S Choi, M H Cardone
1Biomaterials Science and Engineering Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
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.
Insights
Asiatic acid induces glioblastoma cell death through both apoptosis and necrosis. Calcium (Ca2+) signaling plays a critical role, with Ca2+-mediated necrosis being the predominant cell death pathway.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Asiatic acid (AA), a triterpene, exhibits known cytotoxicity against various cancer cell lines.
- Glioblastoma is an aggressive brain tumor with limited treatment options.
Purpose of the Study:
- To investigate the mechanisms of Asiatic acid-induced cell death in U-87 MG human glioblastoma cells.
- To determine the specific pathways involved in AA-induced glioblastoma cell death, including apoptosis and necrosis.
Main Methods:
- Treatment of U-87 MG glioblastoma cells with varying doses and durations of Asiatic acid.
- Assessment of cell death via apoptosis and necrosis assays.
- Measurement of mitochondrial membrane potential, caspase activation, and intracellular free Ca2+ levels.
- Inhibition studies using caspase inhibitor zVAD-fmk and Ca2+ inhibitor BAPTA/AM.
Main Results:
- Asiatic acid induced dose- and time-dependent cell death in U-87 MG glioblastoma cells, involving both apoptosis and necrosis.
- AA-induced cell death was linked to reduced mitochondrial membrane potential, activated caspases (-9 and -3), and elevated intracellular Ca2+.
- While caspase inhibition blocked caspase activation, it did not prevent cell death, whereas Ca2+ inhibition significantly reduced AA-induced cell death.
- AA-induced cell death in colon cancer RKO cells was predominantly apoptotic, suggesting cell-type specificity.
Conclusions:
- Asiatic acid triggers glioblastoma cell death through a combination of apoptotic and necrotic pathways.
- Intracellular calcium (Ca2+) signaling is a key mediator of AA-induced glioblastoma cell death, with necrosis predominating.
- The findings highlight the complex role of Ca2+ in mediating triterpene-induced cancer cell death.
