Wang Jinhong, Xie Hai, Gao Feng, Zhao Tingkun, Yang Hongming, Kang Bai
Department of Pharmacology, Weifang Medical University, Weifang, 261053, China.
Department of Nuclear Medicine, Weifang Medical University, Weifang, 261053, China.
Tumour Biol. 2016 Mar;37(3):4203-12. doi: 10.1007/s13277-015-4029-3. Epub 2015 Oct 22.
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 (Hep3B(TAp73/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 Hep3B(TAp73/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.
姜黄素在多种肿瘤中具有抗癌作用。研究表明，它可通过p53依赖的途径诱导细胞凋亡。p73基因是p53家族的成员，其编码一种肿瘤抑制因子（具有转录激活能力的p73（TAp73））和一种假定的癌基因（显性负性p73（DNp73））；前者与肿瘤抑制因子p53具有相似性，而后者作为显性负性蛋白，可干扰TAp73的活性。为了了解姜黄素诱导细胞凋亡过程中涉及的p73依赖机制，我们使用p53缺陷的Hep3B细胞（Hep3B(TAp73/DNp73)）建立了p73过表达细胞模型。我们的结果表明，40和80μM浓度的姜黄素可诱导DNA损伤，增加TAp73/DNp73比值，并导致Hep3B(TAp73/DNp73)细胞凋亡。凋亡性细胞死亡与线粒体膜电位丧失、细胞色素c从线粒体释放以及半胱天冬酶9、半胱天冬酶3和聚（ADP-核糖）聚合酶（PARP）的裂解同时发生。这些结果证明了姜黄素诱导细胞凋亡的p73依赖机制，该机制涉及线粒体介导的途径。
