2. Academic Validation
  3. The ROS/NF-κB/HK2 axis is involved in the arsenic-induced Warburg effect in human L-02 hepatocytes

The ROS/NF-κB/HK2 axis is involved in the arsenic-induced Warburg effect in human L-02 hepatocytes

  • Int J Environ Health Res. 2022 Oct 20;1-16. doi: 10.1080/09603123.2022.2134559.
Fanshuo Yin 1 2,  Ying Zhang 1 2,  Xin Zhang 1 2,  Meichen Zhang 1 2,  Zaihong Zhang 1 2,  Yunyi Yin 1 2,  Haili Xu 1 2,  Yanmei Yang 1,  Yanhui Gao 1
Affiliations

Affiliations

  • 1 Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang, China.
  • 2 Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health of P. R. China, Harbin Medical University, Harbin, Heilongjiang, China.
PMID: 36264688 DOI: 10.1080/09603123.2022.2134559
Abstract

Arsenic has been identified as a carcinogen, although the molecular mechanism underlying itscarcinogenesis has not been fully elucidated. To date, only a few studies have attempted to confirm a direct link between oxidative stress and the Warburg effect . This study demonstrated that 0.2 μmol/L As3+ induced the Warburg effect to contribute to abnormal proliferation of L-02 cells, that was mediated by upregulation of Hexokinase 2 (HK2), a key Enzyme in glycolysis. Further study indicated that arsenic-induced accumulation of Reactive Oxygen Species (ROS) activated the nuclear factor kappa B (NF-κB) signaling pathway by phosphorylation of p65 at the Ser536 and Ser276 sites, leading to upregulated expression of HK2. We therefore concluded that the ROS/NF-κB/HK2 axis contributes to the Warburg effect and cell proliferation induced by low doses of arsenic.AbbreviationsROS, Reactive oxygen species; NAC, N-acetyl-L-cysteine; 2-DG, 2-deoxy-D-glucose; 2-NBDG, 2-Deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-D-glucose.

Keywords

Arsenic; Warburg effect; cell proliferation; hexokinase 2; nuclear factor kappa B; reactive oxygen species.

Figures
Products