Curcumin Induces Apoptosis of Upper Aerodigestive Tract Cancer Cells by Targeting Multiple Pathways
Curcumin Induces Apoptosis of Upper Aerodigestive Tract Cancer Cells by Targeting Multiple Pathways
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DOI：
10.1371/journal.pone.0124218
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发表时间：
2015-04-24
期刊：
影响因子：
3.7
通讯作者：
Shin, Dong Moon
中科院分区：
文献类型：
--
作者：
Amin, A. R. M. Ruhul;Haque, Abedul;Shin, Dong Moon
姜黄素是一种从印度香料“Haldi”或“咖喱粉”中分离出来的天然化合物，几个世纪以来一直被用作许多疾病的传统疗法。最近，姜黄素在癌症预防和治疗中的潜在用途促使研究揭示与其抗肿瘤作用相关的分子机制。在目前的手稿中，我们研究了姜黄素诱导上呼吸消化道癌细胞系凋亡的机制，并表明姜黄素诱导的凋亡是由多个途径的调节介导的，如诱导p73，抑制p-AKT和Bcl-2。用姜黄素处理细胞诱导头颈癌和肺癌细胞系中的p53和相关蛋白p73。显性失活p73的p73显着保护姜黄素诱导的细胞凋亡，而消融p53的shRNA没有效果。姜黄素处理还强烈抑制p-AKT和Bcl-2，并且组成性活性AKT或Bcl-2的过表达显著抑制姜黄素诱导的细胞凋亡。总之，我们的研究结果表明，姜黄素诱导的细胞凋亡是通过激活肿瘤抑制基因p73和抑制p-AKT和Bcl-2介导的。
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.