Curcumin, a natural polyphenol antioxidant extracted from the root of turmeric (Curcuma longa), can induce apoptosis and DNA demethylation in several types of cancer cells. However, the mechanism of its anticancer potentials and DNA demethylation effects and the potential relationships between these outcomes have not been clearly elucidated. In the present study, the effects of curcumin on the proliferation, colony formation, and migration of human gastric cancer cells (hGCCs) were explored. Reactive oxygen species (ROS) levels, mitochondrial damage, DNA damage, and apoptosis of curcumin-treated hGCCs were analyzed. Changes in the expression of several genes related to DNA damage repair, the p53 pathway, cell cycle, and DNA methylation following curcumin treatment were also evaluated. We observed that curcumin inhibited the proliferation, colony formation, and migration of hGCCs in a dose- and time-dependent fashion. A high concentration of curcumin elevated ROS levels and triggered mitochondrial damage, DNA damage, and apoptosis of hGCCs. Further, curcumin-induced DNA demethylation of hGCCs was mediated by the damaged DNA repair-p53-p21/GADD45A-cyclin/CDK-Rb/E2F-DNMT1 axis. We propose that the anticancer effect of curcumin could largely be attributed to its prooxidative effect at high concentrations and ROS elevation in cancer cells. Moreover, we present a novel mechanism by which curcumin induces DNA demethylation of hGCCs, suggesting the need to further investigate the demethylation mechanisms of other DNA hypomethylating drugs.

中文翻译：

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姜黄素诱导的人类胃癌细胞DNA脱甲基是通过DNA损伤反应途径介导的。

姜黄素，一种从姜黄的根中提取的天然多酚抗氧化剂（姜黄）），可以在几种类型的癌细胞中诱导凋亡和DNA去甲基化。但是，其抗癌潜力和DNA脱甲基作用的机制以及这些结果之间的潜在关系尚未清楚阐明。在本研究中，研究了姜黄素对人胃癌细胞（hGCC）增殖，集落形成和迁移的影响。分析了姜黄素处理的hGCC的活性氧（ROS）水平，线粒体损伤，DNA损伤和凋亡。姜黄素处理后，还评估了与DNA损伤修复，p53途径，细胞周期和DNA甲基化相关的几种基因的表达变化。我们观察到姜黄素以剂量和时间依赖性方式抑制hGCC的增殖，集落形成和迁移。高浓度姜黄素会升高ROS水平，并触发线粒体损伤，DNA损伤和hGCC凋亡。此外，姜黄素诱导的hGCC DNA脱甲基是由受损的DNA修复-p53-p21 / GADD45A-cyclin / CDK-Rb / E2F-DNMT1轴介导的。我们提出姜黄素的抗癌作用在很大程度上可以归因于其在高浓度时的促氧化作用和癌细胞中ROS的升高。此外，我们提出了一种新的机制，姜黄素可通过该机制诱导hGCC的DNA脱甲基，这表明需要进一步研究其他DNA低甲基化药物的脱甲基机制。姜黄素诱导的hGCC DNA脱甲基由受损的DNA修复-p53-p21 / GADD45A-cyclin / CDK-Rb / E2F-DNMT1轴介导。我们提出姜黄素的抗癌作用在很大程度上可以归因于其在高浓度时的促氧化作用和癌细胞中ROS的升高。此外，我们提出了一种新的机制，姜黄素可通过该机制诱导hGCC的DNA脱甲基，这表明需要进一步研究其他DNA低甲基化药物的脱甲基机制。姜黄素诱导的hGCC DNA脱甲基由受损的DNA修复-p53-p21 / GADD45A-cyclin / CDK-Rb / E2F-DNMT1轴介导。我们提出姜黄素的抗癌作用在很大程度上可以归因于其在高浓度时的促氧化作用和癌细胞中ROS的升高。此外，我们提出了一种新的机制，姜黄素可通过该机制诱导hGCC的DNA脱甲基，这表明需要进一步研究其他DNA低甲基化药物的脱甲基机制。