Curcumin induces apoptosis and cell cycle arrest via the activation of reactive oxygen species-independent mitochondrial apoptotic pathway in Smad4 and p53 mutated colon adenocarcinoma HT29 cells
Curcumin induces apoptosis and cell cycle arrest via the activation of reactive oxygen species-independent mitochondrial apoptotic pathway in Smad4 and p53 mutated colon adenocarcinoma HT29 cells
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DOI：
10.1016/j.nutres.2017.12.011
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发表时间：
2018-03-01
影响因子：
4.5
通讯作者：
Sivalingam, Nageswaran
中科院分区：
文献类型：
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作者：
Agarwal, Ayushi;Kasinathan, Akiladdevi;Sivalingam, Nageswaran
(C)姜黄素是一种天然的膳食多酚化合物，对肿瘤细胞具有多种药理活性，如抗增殖和防癌活性。事实上，姜黄素产生的活性氧（ROS）在结肠癌细胞死亡和细胞增殖抑制中的作用尚不清楚。在本研究中，我们假设姜黄素诱导的ROS可能促进结肠癌细胞凋亡和细胞周期阻滞。为了验证这一假说，我们在Smd4和p53突变的HT-29结肠癌细胞中研究了姜黄素诱导ROS的凋亡诱导潜能和细胞周期抑制作用。我们发现姜黄素处理显著增加HT-29细胞中的ROS水平，并呈剂量和时间依赖性。此外，姜黄素处理显著降低HT-29细胞的细胞活力和增殖潜力，并呈剂量和时间依赖性。相反，n -乙酰半胱氨酸处理消除了ROS的产生和姜黄素对HT-29细胞的抑制作用。此外，姜黄素处理未显示出对HT-29细胞的任何细胞毒性作用。此外，姜黄素诱导的ROS产生导致HT-29细胞DNA断裂、染色质凝聚和细胞核收缩，并以剂量和时间依赖的方式显著增加凋亡细胞。然而，n-乙酰半胱氨酸预处理抑制姜黄素诱导的HT-29细胞ROS的凋亡触发作用。此外，姜黄素诱导的ROS可有效介导HT-29细胞的细胞周期抑制。总之，我们的数据提供了姜黄素在携带Smad4和p53突变的结肠癌细胞中诱导ROS非依赖性细胞凋亡和细胞周期阻滞的第一个证据。(C) 2018爱思唯尔公司版权所有。
(C)urcumin is a natural dietary polyphenol compound that has various pharmacological activities such as antiproliferative and cancer-preventive activities on tumor cells. Indeed, the role reactive oxygen species (ROS) generated by curcumin on cell death and cell proliferation inhibition in colon cancer is poorly understood. In the present study, we hypothesized that curcumin-induced ROS may promote apoptosis and cell cycle arrest in colon cancer. To test this hypothesis, the apoptosis-inducing potential and cell cycle inhibition effect of ROS induced by curcumin was investigated in Smd4 and p53 mutated HT-29 colon adenocarcinoma cells. We found that curcumin treatment significantly increased the level of ROS in HT-29 cells in a dose- and time-dependent manner. Furthermore, curcumin treatment markedly decreased the cell viability and proliferation potential of HT-29 cells in a dose- and time-dependent manner. Conversely, generation of ROS and inhibitory effect of curcumin on HT-29 cells were abrogated by N-acetylcysteine treatment. In addition, curcumin treatment did not show any cytotoxic effects on HT-29 cells. Furthermore, curcumin-induced ROS generation caused the DNA fragmentation, chromatin condensation, and cell nuclear shrinkage and significantly increased apoptotic cells in a dose- and time-dependent manner in HT-29 cells. However, pretreatment of N-acetylcysteine inhibited the apoptosis-triggering effect of curcumin-induced ROS in HT-29 cells. In addition, curcumin-induced ROS effectively mediated cell cycle inhibition in HT-29 cells. In conclusion, our data provide the first evidence that curcumin induces ROS independent apoptosis and cell cycle arrest in colon cancer cells that carry mutation on Smad4 and p53. (C) 2018 Elsevier Inc. All rights reserved.