Chaetocin induces cell cycle arrest and apoptosis by regulating the ROS-mediated ASK-1/JNK signaling pathways

: The present study demonstrated that chaetocin, a natural small-molecule product produced by Chaetomium fungal species and a potential anticancer agent, inhibited the viability and invasive ability of the human intrahepatic cholangio-carcinoma cell line CCLP-1 in vivo and in vitro as revealed by CCK-8 and Transwell invasion assays and mouse xenograft tumor experiments. As determined using flow cytometry and intracellular ROS assays, chaetocin was found to induce cell cycle arrest and oxidative stress, leading to CCLP-1 cell apoptosis. Cell apoptosis can be initiated via different apoptotic signaling pathways under oxidative stress. As determined by western blot analysis, expression levels of the apoptosis signal-regulating kinase 1 (ASK-1) signalosome and its downstream c-Jun N-terminal kinase (JNK) signaling pathway were increased under oxidative stress stimulation. These findings indicate that chaetocin arrests the cell cycle and induces apoptosis by regulating the reactive oxygen species-mediated ASK-1/JNK signaling pathways.