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Updated: Jan 14, 2026

Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
Published on: February 6, 2015
Hydrogen peroxide and cisplatin regulate the ROS/PKM2 pathway to affect the growth of cancer
Li-Yuan Bai1,2, Chang-Fang Chiu1,3, Chia-Yung Wu1
1Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital Taichung 404, Taiwan.
Abstract:
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 N-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.
Insights
Reactive oxygen species (ROS) induce cancer cell death. Pyruvate kinase M2 (PKM2) nuclear levels decrease with ROS-inducing treatments, suggesting PKM2 as a potential anticancer target.
Area of Science:
- Oncology
- Biochemistry
- Cell Biology
Background:
- Aberrant reactive oxygen species (ROS) production contributes to DNA damage, chronic diseases, and cancer.
- Pyruvate kinase M2 (PKM2), an enzyme crucial for glycolysis and energy metabolism, is overexpressed in various malignancies.
Purpose of the Study:
- To investigate the impact of ROS-inducing agents on cancer cells and the role of PKM2.
- To explore the potential of targeting PKM2 in anticancer therapy.
Main Methods:
- Induction of ROS using hydrogen peroxide (H2O2) and cisplatin in pancreatic, oral, gastric, and hepatocellular carcinoma cells.
- Assessment of apoptosis and nuclear p-PKM2 levels.
- Evaluation of antioxidant effects using N-acetylcysteine (NAC).
Main Results:
- H2O2 and cisplatin treatments induced ROS production and apoptosis across four cancer cell types.
- Antioxidant NAC partially reduced H2O2- and cisplatin-induced apoptosis.
- Nuclear p-PKM2 levels were downregulated by H2O2 and cisplatin, with levels restored by NAC.
Conclusions:
- PKM2 nuclear downregulation is associated with ROS-induced apoptosis in cancer cells.
- PKM2 may serve as a potential therapeutic target for anticancer strategies.
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