Aurora kinases are Ser/Thr kinases that function as mitotic regulators. 5-Methoxy-2-(2-methoxynaphthalen-1-yl)-4H-chromen-4-one (DK1913) is a synthetic pan-Aurora kinase inhibitor. However, the mode of action of DK1913 concerning the induction of apoptosis is unclear. Here, we report that DK1913 triggered apoptosis, as revealed by flow cytometry and Annexin V staining. DK1913 enhanced the intracellular levels of reactive oxygen species (ROS) and stimulated the endoplasmic reticulum (ER) and genotoxic stress responses. We also found that DK1913 induced the loss of mitochondrial membrane potential, leading to the activation of caspase-9, caspase-7, and caspase-3. In addition, the antioxidant, butylated hydroxyanisole (BHA), abrogated DK1913-induced loss of mitochondrial membrane potential and activation of the caspase cascade. These findings demonstrate that pan-Aurora kinase inhibitor DK1913 triggers apoptosis through ROS-mediated ER and genotoxic stress responses.

中文翻译：

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一种合成的 Pan-Aurora 激酶抑制剂，5-Methoxy-2-(2-methoxynaphthalen-1-yl)-4H-chromen-4-one，在 HCT116 结肠癌细胞中触发反应性氧种介导的细胞凋亡

极光激酶是丝氨酸/苏氨酸激酶，起到有丝分裂调节剂的作用。5-Methoxy-2-(2-methoxynaphthalen-1-yl)-4H-chromen-4-one (DK1913) 是一种合成的泛极光激酶抑制剂。然而，关于诱导细胞凋亡的DK1913的作用方式尚不清楚。在这里，我们报告了 DK1913 触发细胞凋亡，如流式细胞术和膜联蛋白 V 染色所揭示的。DK1913 提高细胞内活性氧 (ROS) 的水平并刺激内质网 (ER) 和基因毒性应激反应。我们还发现 DK1913 诱导线粒体膜电位的丧失，导致 caspase-9、caspase-7 和 caspase-3 的激活。此外，抗氧化剂丁基羟基茴香醚 (BHA) 消除了 DK1913 诱导的线粒体膜电位丧失和半胱天冬酶级联反应的激活。