Narciclasine induces autophagy-dependent apoptosis in triple-negative breast cancer cells by regulating the AMPK-ULK1 axis.

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.

• Authors: Chuan Cao, Wei Huang, Nan Zhang, Fengbo Wu, Ting Xu, Xiaoli Pan, Cheng Peng, Bo Han
• Journal: Cell proliferation (Cell Prolif) Vol. 51 Issue 6 Pg. e12518 (Dec 2018) ISSN: 1365-2184 [Electronic] England
• PMID: 30152053 (Publication Type: Journal Article)
• Copyright: © 2018 John Wiley & Sons Ltd.

Chemical References

• Amaryllidaceae Alkaloids
• Intracellular Signaling Peptides and Proteins
• Phenanthridines
• narciclasine
• Autophagy-Related Protein-1 Homolog
• ULK1 protein, human

Topics

• Amaryllidaceae Alkaloids (pharmacology)
• Apoptosis (drug effects)
• Autophagy (drug effects)
• Autophagy-Related Protein-1 Homolog (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Female
• Humans
• Intracellular Signaling Peptides and Proteins (drug effects)
• Phenanthridines (pharmacology)
• Triple Negative Breast Neoplasms (drug therapy)