Alteronol induces cell cycle arrest and apoptosis via increased reactive oxygen species production in human breast cancer T47D cells. (7th February 2018)

• Record Type: Journal Article
• Authors: Ren, Boxue; Li, Defang; Si, Lingling; Ding, Yangfang; Han, Jichun; Chen, Xiaoyu; Zheng, Qiusheng
• Is Part Of: Journal of pharmacy and pharmacology. Volume 70:Number 4(2018)
• Page Start: 516
• Page End: 524
• Publication Date: 2018-02-07
• Subjects: alteronol -- cell cycle -- G2-phase arrest -- T47D cells; Pharmacy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1111/jphp.12879
• Languages: English
• ISSNs: 0022-3573

Abstract

Abstract: Objective: Emerging evidence showed that alteronol has a potential antitumour effect in several tumour cells. However, the antitumour effect of alteronol on breast cancer has not been reported. This study investigated the mechanisms of alteronol-induced cell proliferation inhibition in human breast cancer T47D cells. Methods: After treatment with alteronol, T47D cell proliferation was examined by MTT assay. The cell cycle distribution, cell apoptosis, reactive oxygen species level and mitochondrial membrane potential were evaluated via flow cytometry. Next, the protein levels of cyclin B1, cdc2, p21, p-cyclin B1, p-cdc2, p53, Bax, Bcl-2 and cytochrome c were analysed using Western blot analysis. Meanwhile, the mRNA levels of cyclin B1, cdc2, p21 and p53 were examined by qRT-PCR. Key findings: Our data showed that alteronol inhibited the proliferation of T47D cells via inducing G2-phase arrest and cell apoptosis. Compared with control group, alteronol significantly increased ROS level and triggered mitochondrial dysfunction in alteronol-treated T47D cells. Further studies showed that the mRNA and protein levels of cdc2 and cyclin B1 were downregulated, while the mRNA and protein levels of p21, p53, p-cyclin B1, p-cdc2 and cytochrome c were upregulated. In addition, the expression level of Bax was increased, and the expression level of Bcl-2 was decreased. Conclusions: Alteronol induced T47D cell cycle arrest and cell apoptosis through increasing ROS production and triggering mitochondrial dysfunction, and subsequently inhibiting T47D cell proliferation.