CBL0137 activates ROS/BAX signaling to promote caspase-3/GSDME-dependent pyroptosis in ovarian cancer cells

• DOI: 10.1016/j.biopha.2023.114529
• Publication Date: 2023-03-14T23:18:38Z
• Authors: Chang Yang; Zhi-Qiang Wang; Zhao-Cong Zhang; Ge Lou; Wei-Lin Jin
• Keywords: Pyroptosis

Curaxin CBL0137 was designed to regulate p53 and nuclear factor-κB simultaneously exhibits antitumor activity by inhibiting tumor cell proliferation inducing apoptosis in multiple cancers. However, whether can induce pyroptosis has not yet been reported. This study demonstrated that induces caspase-3/gasdermin E (GSDME)-dependent via the reactive oxygen species (ROS)/BAX pathway. In ovarian cancer cells, inactivated chromatin remodeling complex which could facilitate transcription, leading decreased transcription of antioxidant genes oxidation causing increased ROS levels. BAX recruited on mitochondrial membrane induced release cytochrome c cleave caspase-3. led cleavage N-terminal GSDME form pores pyroptosis. Results vivo experiments revealed also had anti-tumor effects cells vivo. Our outcomes reveal mechanisms targets indicate is a promising therapeutic agent for cancer.