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The novel role of TRPV2 in promoting the cytotoxicity of H2O2-mediated oxidative stress in human hepatoma cells have been discovered by GIBH scientists

Carcinogenesis is a multistep complicated process in which oxidative stress is considered as an important risk factor for cancer occurrence and progression. DNA and cells of the human body are constantly exposed to exogenous or endogenous attacks such as radiations, chemicals, chronic inflammation, etc, which can lead to an imbalance between oxidants and antioxidants and increase the accumulation of reactive oxygen species (ROS; such as O2·, H2O2, ·OH, etc). ROS interact with the biological molecules and disrupt the normal synthesis and repair of DNA. Constant exposure to DNA lesions can increase the risk of genomic instability and finally lead to malignant transformations.

 

Oxidative stress is important for the initiation and progression of cancers, which confers the cells with a survival advantage by inducing oxidative adaption and drug resistance. Therefore, developing strategies to promote oxidative stress-induced cytotoxicity could be important for cancer therapy. Transient receptor potential vanilloid type 2 (TRPV2) is a non-selective cation channel belonging to the TRPV subfamily. Prof Li Zhiyuan’s group found that H2O2-mediated oxidative stress increases TRPV2 expression in human hepatoma (HepG2 and Huh-7) cells. This occurred at the mRNA and protein levels in a dose-dependent manner. The significance of TRPV2 in promoting H2O2-induced cell death was demonstrated in gain and loss of function studies with overexpression and knockdown of TRPV2, respectively. Mechanistically, H2O2-induced cell death involves inhibition of pro-survival signaling proteins (Akt, Nrf2) and activation of pro-death signaling proteins (p38, JNK1). Overexpression of TRPV2 in H2O2-treated hepatoma cells aggravates the inhibition of Akt and Nrf2, while it enhances the activation of p38 and JNK1 at the early stage of cell death.Interestingly, increased expression of TRPV2 in HepG2 cells improved the efficacy of stress-associated chemicals to induce cell death. The findings of Prof Li’s group suggest that TRPV2 acts as an important enhancer for H2O2-induced cytotoxicity. This process occurred by the inhibition of Akt and Nrf2 as well as the early activation of p38 and JNK1. Prof Li and his group discovered the novel role of TRPV2 as an enhancer of H2O2-induced cytotoxicity, which may provide implacations for exploring a new strategy to inhibit the resistance of hepatoma cells to therapeutic regiments.

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