Effects of alpha-lipoic acid on cell proliferation and apoptosis in MDA-MB-231 human breast cells

ABSTRACT

The role that antioxidants play in the process of carcinogenesis has recently gained considerable attention. alpha-Lipoic acid, a naturally occurring disulfide molecule, is a powerful antioxidant that reportedly exerts beneficial effects in patients with advanced cancer by reducing the level of reactive oxygen species and increasing glutathione peroxidase activity. In this study, we examined changes in the protein and mRNA expression associated with cell proliferation and apoptosis in MDA-MB-231 breast cancer cultured in the presence of various concentrations (0, 250, 500, and 1000 micromol/L) of alpha-lipoic acid. The results revealed that alpha-lipoic acid inhibited the growth of breast cancer cells in a dose-independent manner (P < 0.05). Additionally, ErbB2 and ErbB3 protein and mRNA expressions were significantly decreased in a dose-dependent manner in response to alpha-lipoic acid (P < 0.05). Furthermore, the protein expression of phosphorylated Akt (p-Akt) levels and total Akt, and the mRNA expression of Akt were decreased dose-dependently in cells that were treated with alpha-lipoic acid (P < 0.05). Bcl-2 protein and mRNA expressions were also decreased in cells that were treated with alpha-lipoic acid (P < 0.05). However, Bax protein and mRNA expressions were increased in cells treated with alpha-lipoic acid (P < 0.05). Finally, caspase-3 activity was significantly increased in a dose-dependent manner in cells treated with alpha-lipoic acid (P < 0.05). In conclusion, we demonstrated that alpha-lipoic acid inhibits cell proliferation and induces apoptosis in MDA-MB-231 breast cancer cell lines.