α-Lipoic acid reduces matrix metalloproteinase activity in MDA-MB-231 human breast cancer cells

Abstract 

α-Lipoic acid (LA), a naturally occurring molecule in animal and plant cells, is a potent antioxidant that reportedly exerts beneficial effects on cell proliferation and apoptosis in various cancer cell lines. However, the molecular mechanisms behind the antimetastatic property of LA are not well understood. The present study investigates the effect of LA on metastasis in a cell system. Our hypothesis is that LA inhibits metastasis via inhibition of matrix metalloproteinase (MMP) in vitro. MDA-MB-231 cells, a human breast cancer cell line, were treated with various concentrations of LA (0, 250, 500, or 1000 μmol/L) to measure metastasis, MMP activity, and mRNA expression. The viability of cells was examined by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. The effect of LA on metastasis was evaluated using the motility, migration, and invasion assay in vitro. The activity and mRNA expression of MMP-2 and MMP-9 were measured. After LA treatment, cell motility and cell migration were significantly decreased (P < .05). α-Lipoic acid also reduced cell invasion through a Matrigel-coated chamber (P < .05). Activities of MMP-2 and MMP-9 were decreased by LA treatment in a dose-dependent manner. RT-PCR analysis confirmed the reduction in mRNA expression level of MMP-2 and MMP-9 by LA treatment. We conclude that in this cell culture model, LA treatment inhibits cancer metastasis, and this inhibition is likely due to the decrease in the activity and mRNA expression levels of MMP-2 and MMP-9 caused by LA.

Abbreviations: ECM, extracellular matrix, FBS, fetal bovine serum, LA, α-Lipoic acid, MMP, matrix metalloproteinase, SFM, serum-free media

Keywords: α-Lipoic acid, Metastasis, Breast cancer cells, MMP-2, MMP-9