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

Cell Proliferation
Chuan CaoBo Han

Abstract

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. 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. 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. Our findings suggest that narciclasine regulates the AMPK-ULK1 signalling axi...Continue Reading

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Citations

Mar 13, 2020·Cell Proliferation·Xiaoru ShaoYunfeng Lin
Jul 31, 2019·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·Z WuJ Jin
Apr 3, 2020·Scientific Reports·Ramakrishnan GopalakrishnanPreet M Chaudhary
Nov 22, 2019·International Journal of Biological Macromolecules·Shuping JiangZhijun Luo
Jul 2, 2021·Biological & Pharmaceutical Bulletin·Daping FanSiying Qu
Jun 21, 2020·Anti-cancer Agents in Medicinal Chemistry·Milad AshrafizadehAmirhossein Sahebkar

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