Conclusions
Our findings suggest that narciclasine regulates the AMPK-ULK1 signalling axis to promote autophagy-dependent apoptosis, demonstrating therapeutic potential against TNBC.
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.