Amin A R M Ruhul, Haque Abedul, Rahman Mohammad Aminur, Chen Zhuo Georgia, Khuri Fadlo Raja, Shin Dong Moon
Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, 30322, United States of America.
PLoS One. 2015 Apr 24;10(4):e0124218. doi: 10.1371/journal.pone.0124218. eCollection 2015.
Curcumin, a natural compound isolated from the Indian spice "Haldi" or "curry powder", has been used for centuries as a traditional remedy for many ailments. Recently, the potential use of curcumin in cancer prevention and therapy urges studies to uncover the molecular mechanisms associated with its anti-tumor effects. In the current manuscript, we investigated the mechanism of curcumin-induced apoptosis in upper aerodigestive tract cancer cell lines and showed that curcumin-induced apoptosis is mediated by the modulation of multiple pathways such as induction of p73, and inhibition of p-AKT and Bcl-2. Treatment of cells with curcumin induced both p53 and the related protein p73 in head and neck and lung cancer cell lines. Inactivation of p73 by dominant negative p73 significantly protected cells from curcumin-induced apoptosis, whereas ablation of p53 by shRNA had no effect. Curcumin treatment also strongly inhibited p-AKT and Bcl-2 and overexpression of constitutively active AKT or Bcl-2 significantly inhibited curcumin-induced apoptosis. Taken together, our findings suggest that curcumin-induced apoptosis is mediated via activating tumor suppressor p73 and inhibiting p-AKT and Bcl-2.
姜黄素是从印度香料“哈尔迪”或“咖喱粉”中分离出的一种天然化合物，几个世纪以来一直被用作治疗多种疾病的传统药物。最近，姜黄素在癌症预防和治疗方面的潜在用途促使人们开展研究，以揭示与其抗肿瘤作用相关的分子机制。在本手稿中，我们研究了姜黄素诱导上消化道癌细胞系凋亡的机制，结果表明，姜黄素诱导的凋亡是由多种信号通路的调节介导的，如诱导p73以及抑制p-AKT和Bcl-2。用姜黄素处理细胞可诱导头颈癌和肺癌细胞系中的p53及相关蛋白p73。用显性负性p73使p73失活可显著保护细胞免受姜黄素诱导的凋亡，而用短发夹RNA（shRNA）消除p53则没有效果。姜黄素处理还能强烈抑制p-AKT和Bcl-2，组成型活性AKT或Bcl-2的过表达可显著抑制姜黄素诱导的凋亡。综上所述，我们的研究结果表明，姜黄素诱导的凋亡是通过激活肿瘤抑制因子p73以及抑制p-AKT和Bcl-2来介导的。
