Eicosapentaenoic acid enhanced apoptotic and oxidant effects of cisplatin via activation of TRPM2 channel in brain tumor cells


CHEMICO-BIOLOGICAL INTERACTIONS, vol.359, 2022 (Peer-Reviewed Journal) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 359
  • Publication Date: 2022
  • Doi Number: 10.1016/j.cbi.2022.109914
  • Journal Indexes: Science Citation Index Expanded, Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Keywords: Apoptosis, Cisplatin, Eicosapentaenoic acid, Glioblastoma, Oxidative stress, TRPM2 channel, OXIDATIVE STRESS, FATTY-ACIDS, MOLECULAR PATHWAYS, NEUROPATHIC PAIN, CANCER CELLS, MITOCHONDRIA, COMBINATION, DAMAGE


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.