Curcumin induces apoptosis in p53-null Hep3B cells through a TAp73/DNp73-dependent pathway

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• 作者：Jinhong Wang ; Hai Xie ; Feng Gao ; Tingkun Zhao ; Hongming Yang ; Bai Kang
• 刊名：Tumor Biology
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：37
• 期：3
• 页码：4203-4212
• 全文大小：555 KB
• 刊物主题：Cancer Research;
• 出版者：Springer Netherlands
• ISSN：1423-0380
• 卷排序：37

文摘

Curcumin has anticancer functions in various tumors. It has been shown to induce apoptosis through p53-dependent pathways. p73 gene is a member of the p53 family which encodes both a tumor suppressor (transactivation-competent p73 (TAp73)) and a putative oncogene (dominant-negative p73 (DNp73)); the former shares similarity with the tumor suppressor p53, and the latter behaves as dominant-negative proteins that interfere with the activity of TAp73. To understand the p73-dependent mechanisms that are engaged during curcumin-induced apoptosis, we established a p73 overexpression cell models using p53-deficient Hep3B cells (Hep3BTAp73/DNp73). Our results demonstrated that curcumin at concentrations of 40 and 80 μM induced DNA damage, increased TAp73/DNp73 ratio, and also led to apoptosis in the Hep3BTAp73/DNp73 cells. The apoptotic cell death was concurrent with the loss of mitochondrial membrane potential; release of cytochrome c from mitochondria; and the cleavage of caspase 9, caspase 3, and poly(ADP-ribose) polymerase (PARP). These results demonstrated a p73-dependent mechanism for curcumin-induced apoptosis that involves the mitochondria-mediated pathway.KeywordsCurcuminTAp73DNp73DNA damageApoptosis