Chuan Cao1,2, Wei Huang1, Nan Zhang2, Fengbo Wu2, Ting Xu2, Xiaoli Pan1, Cheng Peng1, Bo Han1,3. 1. State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China. 2. Department of Pharmacy and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China. 3. Department of Chemistry and The RNA Institute, University at Albany, State University of New York, Albany, New York.
Abstract
OBJECTIVES: Autophagy and apoptosis are major types of eukaryotic programmed cell death, and regulating these processes holds promise for treating cancers. In this study, we explored the regulation mechanisms of narciclasine to autophagy and apoptosis processes in triple-negative breast cancer. MATERIALS AND METHODS: Effects of narciclasine on proliferation, apoptosis, and autophagy of HCC-1937 and MDA-MB-231 triple-negative breast cancer (TNBC) cells were assessed using transmission electronic microscopy, flow cytometry following staining with Annexin V-FITC and propidium iodide, RNA sequencing, real-time PCR, and Western blotting. The ability of narciclasine to inhibit growth of human HCC1937 TNBC xenografts in mice was assessed, and potential mechanisms of inhibition were explored using immunohistochemistry. RESULTS: Narciclasine inhibited TNBC cell proliferation and induced autophagy-dependent apoptosis in a dose-dependent manner. These apoptotic effects could be reversed using autophagy inhibitors, including an AMPK inhibitor and ULK1 siRNA. Consistent with these in vitro results, narciclasine significantly inhibited TNBC tumour growth in mice by upregulating autophagy-dependent apoptosis. CONCLUSIONS: Our findings suggest that narciclasine regulates the AMPK-ULK1 signalling axis to promote autophagy-dependent apoptosis, demonstrating therapeutic potential against TNBC.
OBJECTIVES: Autophagy and apoptosis are major types of eukaryotic programmed cell death, and regulating these processes holds promise for treating cancers. In this study, we explored the regulation mechanisms of narciclasine to autophagy and apoptosis processes in triple-negative breast cancer. MATERIALS AND METHODS: Effects of narciclasine on proliferation, apoptosis, and autophagy of HCC-1937 and MDA-MB-231 triple-negative breast cancer (TNBC) cells were assessed using transmission electronic microscopy, flow cytometry following staining with Annexin V-FITC and propidium iodide, RNA sequencing, real-time PCR, and Western blotting. The ability of narciclasine to inhibit growth of human HCC1937 TNBC xenografts in mice was assessed, and potential mechanisms of inhibition were explored using immunohistochemistry. RESULTS:Narciclasine inhibited TNBC cell proliferation and induced autophagy-dependent apoptosis in a dose-dependent manner. These apoptotic effects could be reversed using autophagy inhibitors, including an AMPK inhibitor and ULK1 siRNA. Consistent with these in vitro results, narciclasine significantly inhibited TNBC tumour growth in mice by upregulating autophagy-dependent apoptosis. CONCLUSIONS: Our findings suggest that narciclasine regulates the AMPK-ULK1 signalling axis to promote autophagy-dependent apoptosis, demonstrating therapeutic potential against TNBC.
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