Cisplatin (CiSP) induced-overload Ca2+ entry results in the increase of mitochondrial oxidative stress and apoptosis in the cancer cell. TRPM2 cation channel is gated by the cytosolic ADP-ribose (ADPR) and reactive oxygen species (ROS). The high content of polyunsaturated fatty acid (PUFA) in the brain is a main target of ROS. Eicosapentaenoic acid (EPA) induces oxidant action via the enhance of PUFA content in the glioblastoma (DBTRG) cells. We hypothesized that a combination of CiSP and EPA may offer a potential therapy in the DBTRG cell by exerting the antitumor, oxidant, and apoptotic actions and stimulating Ca2+ influx and TRPM2 activity. In the DBTRG cells, we induced four groups as control, EPA (30 mu M for 24 h), CiSP (25 mu M for 24 h), and CiSP + EPA.