Reactive Oxygen Species Play a Central Role in Hexavalent Chromium-Induced Apoptosis in Hep3B Cells without the Functional Roles of p53 and Caspase-3

Abstract

BACKGROUND/AIMS: Hexavalent chromium [Cr(VI)] and its compounds, which have the extensive application in diverse industries including metallurgy, textile and electroplating, are known to be genotoxic and mutagenic to humans. Although it is supported by a large body of literatures that p53 and caspase-3 played key roles in Cr(VI)-induced cytotoxicity, it is clear that Cr(VI) could induce apoptosis either without activating caspase, or in a p53- independent manner. METHODS: In the present study, by using Z-VAD-fmk to inhibit caspase-3 in p53-deficient Hep3B cells, we explored the effect of Cr(VI) on apoptosis induction and the related mechanisms when the functions of p53 and caspase were simultaneously blocked. RESULTS: We found that Cr(VI) still induced DNA damage, mitochondrial injury, oxidative stress and apoptosis in Hep3B cells without the functional roles of p53 and caspase-3, and the mechanism study revealed that this was in a ROS-dependent manner since NAC co-treatment showed the protective effect against Cr(VI)-induced apoptosis. CONCLUSION: Our research has disclosed the mechanism involved in Cr(VI)-induced cytotoxicity following the loss of p53 and caspase-3 functions and shed light on the importance of using antioxidants for primary and secondary prevention in Cr(VI) occupational exposure populations.