Temozolomide is an
alkylating agent used as the first line of treatment for
glioblastoma. However, chemoresistance to
temozolomide is common in
glioma patients. In addition, there are likely many unknown mechanisms for the anti-
tumor effects of
temozolomide. It is known that an
alkylating agent,
sulfur mustard, activates cytosolic
phospholipase A2 (cPLA₂) releasing
arachidonic acid to suppress
tumors. The present study was performed to elucidate the involvement of cPLA2 in the anti-
tumor mechanisms of
temozolomide. In three
glioblastoma cell lines (GL261, U251MG and T98G), we performed several evaluations including cell viability, cell migration and apoptosis, to study
temozolomide-induced anti-
tumor effects. Further, we evaluated
tumor size in the murine orthotropic
glioblastoma model after
oral administration of
temozolomide. Finally, we investigated the phosphorylation of cPLA2 in GL261 cells treated with
temozolomide, and clarified whether phosphorylation of cPLA2 affects cell growth.
Temozolomide suppressed cell growth and cell migration in
glioblastoma cells in vitro and showed anti-
tumor effect in the murine orthotopic
glioblastoma model in vivo. Furthermore,
temozolomide increased phosphorylation of cPLA2, which was associated with suppression of cell growth. However, in MGMT high-expressing
glioblastoma T98G cells,
temozolomide could not suppress cell growth or cause phosphorylation of cPLA2. These findings indicate that
temozolomide suppressed cell growth partly by phosphorylation of cPLA2 in
glioblastoma cells. In addition, because
temozolomide did not cause phosphorylation of cPLA2 in MGMT high-expressing
glioblastoma T98G cells, phosphorylation of cPLA2 may be caused by
DNA alkylation of
temozolomide.