Cancer and diabetes, the two mitochondria‐related diseases, have recently been linked to silent mating‐type information regulation 2 homolog 3 (SIRT3) activity irregularities. In this study, the effect of metformin, an antidiabetic with anticancer properties, has been evaluated on mitochondrial functionality markers, cell death pathways, and SIRT3 enzyme activity in the colon cancer cell line, HT‐29, and human embryonic kidney cells (HEK 293). HT‐29 cells were treated with metformin (5, 10, 20, 40, and 80 µM) for 24, 48, and 72 h for measuring the IC₅₀ concentration. Reactive oxygen species (ROS) production, apoptosis, mitochondrial membrane potential, SIRT3 activity, and expression were evaluated against the colon cancer cell line, HT‐29. Results indicated a higher ROS production at 6 than 12 h with metformin treatment. Metformin modified the mitochondrial membrane potential, resulting in cell death induction. Results from SIRT3 activity and expression showed that metformin increased its activity and expression in cancer cells. In conclusion, metformin in HT‐29 cells disturbed the mitochondrial activity via increased ROS levels and SIRT3 activity, and these rapid modifications may play a key role in its cytotoxic property.

中文翻译：

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二甲双胍对HT29结肠癌细胞的细胞毒性促成线粒体Sirt3上调

癌症和糖尿病，这是两种与线粒体相关的疾病，最近与沉默的交配型信息调节2同源3（SIRT3）活动异常有关。在这项研究中，已经评估了二甲双胍（一种具有抗癌特性的抗糖尿病药）对结肠癌细胞系，HT-29和人胚胎肾细胞中的线粒体功能标记，细胞死亡途径和SIRT3酶活性的影响（HEK 293 ）。HT-29细胞用二甲双胍（5、10、20、40和80 µM）处理24、48和72小时，以测量IC ₅₀专注。针对结肠癌细胞系HT‐29评估了活性氧（ROS）的产生，凋亡，线粒体膜电位，SIRT3活性和表达。结果表明，二甲双胍治疗后6 h的ROS产生高于12 h。二甲双胍修饰线粒体膜电位，导致细胞死亡诱导。SIRT3活性和表达的结果表明，二甲双胍可增强其在癌细胞中的活性和表达。总之，HT-29细胞中的二甲双胍通过增加ROS水平和SIRT3活性来干扰线粒体活性，而这些快速修饰可能在其细胞毒性中起关键作用。