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Hirsutine induces apoptosis of human breast cancer MDA-MB-231 cells through mitochondrial pathway

HUANG Qi-Wei¹, ZHAI Na-Na¹, Huang Tao^1,*, LI Dao-Ming²

¹Huanghe Science and Technology College, Zhengzhou 450099, China；²Department of Pathology, Zhengzhou University First Affiliated Hospital, Zhengzhou 450052, China

Abstract

The aim of this study was to investigate the effects of hirsutine on apoptosis of breast cancer cells and its possible mechanism. The MCF-10A, MCF-7 and MDA-MB-231 cells were treated with hirsutine at different concentrations for 48 h or incubated with 160 μmol/L hirsutine for 24, 48, and 72 h. The MCF-10A cell line is a non-tumorigenic epithelial cell line, and the MCF-7 and MDA-MB-231 are human breast adenocarcinoma cell lines. CCK-8 assay was employed to detect the cell viability. Flow cytometry was used to assay the apoptosis and mitochondrial membrane potential (MMP). The protein expressions of Bcl-2, Bax, cleaved-caspase 9, cleaved-caspase 3 and cytochrome C (Cyt C) in the MDA-MB-231 cells were detected by Western blotting. The results showed that hirsutine remarkably reduced the viability of MCF-7 and MDA-MB-231 cells in a time- and dose-dependent manner (P < 0.05) with IC50 values of 447.79 and 179.06 μmol/L, respectively. In the MDA-MB-231 cells, hirsutine induced apoptosis and depolarization of MMP (P < 0.05), released Cyt C from mitochondria (P < 0.05), and activated caspase 9 and caspase 3 (P < 0.05). However, these effects induced by hirsutine were all inhibited by cyclosporin A (CsA) (P < 0.05), a specific inhibitor of mitochondrial permeability transition pore (MPTP). In addition, hirsutine down-regulated the protein level of Bcl-2 and up-regulated the protein level of Bax (P < 0.05). These results suggest that hirsutine may induce apoptosis of human breast cancer MDA-MB-231 cells through decreasing the ratio of Bcl-2 to Bax, opening MPTP, releasing Cyt C from mitochondria, and activating caspase 9 and caspase 3.

Key words: hirsutine;;;;

Received: 2017-06-14　　Accepted: 2018-01-24

Corresponding author: 黄涛　　E-mail: hytzn@163.com

DOI: 10.13294/j.aps.2018.0010

Citing This Article：

HUANG Qi-Wei, ZHAI Na-Na, Huang Tao, LI Dao-Ming. Hirsutine induces apoptosis of human breast cancer MDA-MB-231 cells through mitochondrial pathway. Acta Physiol Sin 2018; 70 (1): 40-46 (in Chinese with English abstract).