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Curcumin induced apoptosis is mediated through oxidative stress in mutated p53 and wild type p53 colon adenocarcinoma cell lines

机译:姜黄素诱导的细胞凋亡是通过突变P53和野生型P53结肠腺癌细胞系氧化应激介导的

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摘要

Curcumin has anti-oxidant, anti-cancer and anti-carcinogen property. Our laboratory had previously reported that, curcumin treatment induces reactive oxygen species (ROS) generation in HT-29 cell line, an effect contradictory to its anti-oxidant property. This study evaluates the role of p53 in curcumin mediated ROS generation and cell death. Curcumin induced ROS was determined by 2',7'-dichlorofluorescein and apoptosis by Hoechst33342/PI staining in HT-29 and HCT-116 cell lines. ROS generation occurs within 1 hour of 40μM curcumin treatment and a reduction was observed by third hour in HCT-116 insinuating p53 involvement. N-acetyl cysteine (NAC) pre-treatment effectively quenched ROS and inhibited membrane potential loss in HT-29, but less effective in HCT-116. Mitochondrial membrane potential loss is evident with 10 and 40 μM curcumin in HCT-116 and at 40 μM curcumin in HT-29. Total p53 protein level increase was observed by 24 hours in HCT-116 upon NAC pre-treatment. Our results indicate that curcumin induces ROS mediated cell death in colon adenocarcinoma cell lines and may be mediated via p53.
机译:姜黄素具有抗氧化、抗癌和抗癌的特性。我们的实验室之前曾报道,姜黄素处理可诱导HT-29细胞系产生活性氧(ROS),这种作用与其抗氧化特性相矛盾。本研究评估了p53在姜黄素介导的活性氧生成和细胞死亡中的作用。在HT-29和HCT-116细胞系中,通过2',7'-二氯荧光素和Hoechst3342/PI染色测定姜黄素诱导的ROS和凋亡。在40μM姜黄素治疗后1小时内出现ROS生成,第三小时观察到HCT-116在暗示p53参与的情况下减少。N-乙酰半胱氨酸(NAC)预处理可有效抑制HT-29中的活性氧并抑制膜电位损失,但对HCT-116的效果较差。在HCT-116和HT-29中,10μM和40μM姜黄素的线粒体膜电位损失明显。NAC预处理后24小时,HCT-116中的p53蛋白总水平升高。我们的结果表明,姜黄素在结肠腺癌细胞系中诱导ROS介导的细胞死亡,并且可能通过p53介导。

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