Open AccessNarciclasine induces autophagy‐dependent apoptosis in triple‐negative breast cancer cells by regulating the AMPK‐ULK1 axis
Author(s) -
Cao Chuan,
Huang Wei,
Zhang Nan,
Wu Fengbo,
Xu Ting,
Pan Xiaoli,
Peng Cheng,
Han Bo
Publication year - 2018
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12518
Subject(s) - autophagy , propidium iodide , apoptosis , triple negative breast cancer , annexin , cancer research , ampk , programmed cell death , microbiology and biotechnology , cell growth , chemistry , flow cytometry , biology , cancer , breast cancer , kinase , protein kinase a , biochemistry , genetics
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 HCC 1937 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 ULK 1 si RNA . 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 ‐ ULK 1 signalling axis to promote autophagy‐dependent apoptosis, demonstrating therapeutic potential against TNBC .