A Synthetic Pan-Aurora Kinase Inhibitor, 5-Methoxy-2-(2-methoxynaphthalen-1-yl)-4H-chromen-4-one, Triggers Reactive Oxygen Species-Mediated Apoptosis in HCT116 Colon Cancer Cells

Figure 8

Hypothetical model for DK1913-induced apoptosis. Inhibition of aurora kinases by DK1913 induces the generation of intracellular ROS. Aberrant ROS levels activate the UPR pathway of the ER, leading to the accumulation of transcription factor CHOP, which in turn upregulates the proapoptotic BIM. DK1913-induced genotoxic response induces p53-dependent BAX expression and caspase-2-mediated activation of proapoptotic t-BID. Loss of mitochondrial membrane potential (ΔΨm) along with the accumulation of BAX and BH3-only proteins (BIM and t-BID) facilitates Cyt c release from the mitochondria, which leads to the activation of caspase-9 and caspase-3/7, triggering apoptosis.