Hydrogen peroxide and cisplatin regulate the ROS/PKM2 pathway to affect the growth of cancer

Aberrant production of reactive oxygen species (ROS) cause DNA damage which led to the chronic diseases and cancer. During glycolysis, the enzyme pyruvate kinase M2 (PKM2) is responsible for energy metabolism and its overexpression can be found in various malignancies. To investigate the impact of PKM2 and ROS, hydrogen peroxide (H₂O₂) and cisplatin were used. This study showed that H₂O₂ and cisplatin induced ROS production and apoptosis in these four tumor cells: pancreatic cancer, oral cancer, gastric cancer, and hepatocellular carcinoma. In addition, H₂O₂- and cisplatin-increased apoptosis was partially reduced by pre-treatment with an antioxidant <i>N</i>-acetylcysteine (NAC) in SC-M1 gastric cancer and HSC-3 oral cancer cells. Interestingly, the levels of p-PKM2 in the nucleus were downregulated after treatment with H₂O₂ and cisplatin. This phenomenon was reversed with the combination of NAC. These findings provide PKM2 may be a potential target for anticancer therapy.