Alteronol induces cell cycle arrest and apoptosis via increased reactive oxygen species production in human breast cancer T47D cells

• Published in: Journal of pharmacy and pharmacology 2018-04, Vol.70 (4), p.516-524
• Main Authors: Ren, Boxue, Li, Defang, Si, Lingling, Ding, Yangfang, Han, Jichun, Chen, Xiaoyu, Zheng, Qiusheng
• Format: Article
• Language: English
• Subjects: alteronol; Antineoplastic Agents, Phytogenic - pharmacology; Antineoplastic Agents, Phytogenic - therapeutic use; Apoptosis; Apoptosis - drug effects; Apoptosis - physiology; BAX protein; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Cdc2 protein; Cell cycle; Cell Cycle Checkpoints - drug effects; Cell Cycle Checkpoints - physiology; Cell growth; Cell Line, Tumor; Cell proliferation; Cell Proliferation - drug effects; Cell Proliferation - physiology; Cyclin B1; Cyclin-dependent kinase inhibitor p21; Cytochrome; Cytochrome c; Dose-Response Relationship, Drug; Female; Flow cytometry; G2‐phase arrest; GTP-binding protein; Humans; Membrane potential; Mitochondria; mRNA; Naphthoquinones - pharmacology; Naphthoquinones - therapeutic use; p53 Protein; Proteins; Reactive oxygen species; Reactive Oxygen Species - agonists; Reactive Oxygen Species - metabolism; T47D cells; Tumors
• ISSN: 0022-3573; 2042-7158
• DOI: 10.1111/jphp.12879

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.