α-Lipoic acid inhibits the migration and invasion of breast cancer cells through inhibition of TGFβ signaling

Publication date: 15 August 2018Source: Life Sciences, Volume 207Author(s): Joytirmay Tripathy, Anindita Tripathy, Muthusamy Thangaraju, Mrutyunjay Suar, Selvakumar ElangovanAbstractAimsInvasion and metastasis are the main cause of mortality in breast cancer. Hence, novel therapeutic interventions with high specificity toward invasion and metastasis are necessary. α-Lipoic acid showed antiproliferative and cytotoxic effects on several cancers including breast cancer. However, the effect of lipoic acid on breast cancer metastasis remains unclear.Main methodsIn the present study, we examined the effects of lipoic acid on the migration and invasion of MDA-MB-231 and 4T1 breast cancer cells.Key findingsOur data showed that lipoic acid effectively inhibited the colony forming ability of highly invasive MDA-MB-231 and 4T1 cells. Moreover, the nontoxic concentrations of lipoic acid significantly reduced the migration of breast cancer cells. Lipoic acid also inhibited the TGFβ-induced angiopoietin-like 4 (ANGPTL4) expression and reduced the activity of matrix metalloproteinase-9 (MMP-9), an enzyme involved in invasion and metastasis, in both the cell lines. The inhibition of cell migration by lipoic acid is accompanied by the downregulation of FAK, ERK1/2 and AKT phosphorylation, and inhibition of nuclear translocation of β-catenin.SignificanceOur data demonstrated that lipoic acid inhibited the migration and invasion of metastatic breast cancer cells at least in part through inhi...
Source: Life Sciences - Category: Biology Source Type: research