GADD45β induction by S-adenosylmethionine inhibits hepatocellular carcinoma cell proliferation during acute ischemia-hypoxia

نویسندگان

  • Ding Ma
  • Baiyong Shen
  • Varun Seewoo
  • Hui Tong
  • Weiping Yang
  • Xi Cheng
  • Zhijian Jin
  • Chenghong Peng
  • Weihua Qiu
چکیده

Growth arrest DNA damage-inducible gene 45β (GADD45β), which influences cell growth, apoptosis and cellular response to DNA damage, is downregulated in hepatocellular carcinoma (HCC). S-adenosylmethionine (SAMe) serves as an essential methyl donor in multiple metabolic pathways and is a polyamine and glutathione (GSH) precursor. In this study, we assessed the roles of GADD45β and SAMe in cell survival during acute ischemia-hypoxia (I/H). SAMe treatment induced growth of HL-7702 normal hepatic cells, but decreased the viability of HepG2 (p53 wild-type) and Hep3B (p53 null) HCC cells. Cells were exposed to I/H with or without SAMe pre-treatment. I/H exposure alone triggered HCC cell proliferation promoted by autophagy. SAMe pre-treatment restored GADD45β expression and activated HCC cell apoptosis and eliminated I/H-induced HCC cell proliferation. p53 loss blunted the response to SAMe and I/H exposure in Hep3B cells; thus, the inhibitory effect of SAMe on cell proliferation may be reduced in p53-null cells as compared to wild-type cells. These results indicate that GADD45β induction by SAMe inhibits HCC cell proliferation during I/H as a result of increased apoptosis, and that SAMe also protects normal hepatocytes from apoptotic cell death and promotes normal cell regeneration. SAMe should be considered a potential therapeutic agent for the management of HCC.

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عنوان ژورنال:

دوره 7  شماره 

صفحات  -

تاریخ انتشار 2016