Caspase-3 suppresses diethylnitrosamine-induced hepatocyte death, compensatory proliferation and hepatocarcinogenesis through inhibiting p38 activation

Cell Death & Disease
Na ShangWei Qiu

Abstract

It is critical to understand the molecular mechanisms of hepatocarcinogenesis in order to prevent or treat hepatocellular carcinoma (HCC). The development of HCC is commonly associated with hepatocyte death and compensatory proliferation. However, the role of Caspase-3, a key apoptotic executor, in hepatocarcinogenesis is unknown. In this study, we used Caspase-3-deficient mice to examine the role of Caspase-3 in hepatocarcinogenesis in a chemical (diethylnitrosamine, DEN)-induced HCC model. We found that Caspase-3 deficiency significantly increased DEN-induced HCC. Unexpectedly, Caspase-3 deficiency increased apoptosis induced by DEN and the subsequent compensatory proliferation. Intriguingly, we discovered that Caspase-3 deficiency increased the activation of p38 with and without DEN treatment. Moreover, we demonstrated that TNFα and IL1α stimulated increased activation of p38 in Caspase-3 KO hepatocytes compared with wild-type hepatocytes. Finally, we found that inhibition of p38 by SB202190 abrogated enhanced hepatocyte death, compensatory proliferation and HCC induced by DEN in Caspase-3-deficient mice. Overall, our data suggest that Caspase-3 inhibits chemical-induced hepatocarcinogenesis by suppressing p38 activation and...Continue Reading

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Citations

May 16, 2020·Frontiers in Neurology·Dahao Wu, Changzhen Wang
May 10, 2020·Evidence-based Complementary and Alternative Medicine : ECAM·Zhulin WuLisheng Peng
Mar 16, 2021·Environmental Science and Pollution Research International·Eman A Al-ShahariAbeer A Alm-Eldeen
Jul 30, 2021·Environmental Science and Pollution Research International·Nahed Abdel-AzizMarwa G A Hegazy

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Methods Mentioned

BETA
nuclear translocation
Assay
PCR
electrophoresis

Software Mentioned

GraphPad Prism

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