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

Joytirmay Tripathy, Anindita Tripathy, Muthusamy Thangaraju, Mrutyunjay Suar, Selvakumar Elangovan

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Aims: Invasion 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 methods: In 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 findings: Our 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. Significance: Our data demonstrated that lipoic acid inhibited the migration and invasion of metastatic breast cancer cells at least in part through inhibiting ERK1/2 and AKT signaling. Thus, our findings show that the inhibition of TGFβ signaling is a potential mechanism for the anti-invasive effects of lipoic acid.

Original languageEnglish (US)
Pages (from-to)15-22
Number of pages8
JournalLife sciences
Volume207
DOIs
Publication statusPublished - Aug 15 2018

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Keywords

  • Breast cancer
  • Lipoic acid
  • Matrix metalloproteinase
  • Migration and invasion
  • TGFβ

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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