α-Linolenic Acid Induces Breast Cancer Cell Apoptosis by Down-Regulating Human Fatty Acid Synthase

Abstract

Background/Aims: Fatty acid synthase (FASN) is a multi-enzyme complex that synthesizes endogenous fatty acids. The overexpression of FASN has been reported in variety of cancers, including breast, ovarian, prostrate, and colon cancers, which strongly indicates the involvement of FASN in cancer progression. α-Linolenic acid (ALA) has many biological activities, including anti-cancer effects. The aim of the present study was to investigate the inhibitory effect of ALA on fatty acid synthesis pathway and apoptosis of human breast cancer cells. Methods: Cytotoxicity of ALA in human breast cancer cells (MDA-MB-231 and MCF-7 cells) was assessed by MTT assay. Changes in protein expression were detected by immunoblot analysis. Cell migration was detected by wound healing and cell transwell assay. Apoptotic effects, mitochondrial membrane potential and cell cycle analysis were detected by flow cytometry. Molecular docking was carried out with the AutoDockTools program suite to analyze the binding abilities of ALA on thioesterase (TE) domain of FASN. Results: We found that the expression levels of FASN decreased significantly in ALA treated breast cancer cells. Compared with palmitic acid (PA), ALA reduced cell viability in a dose-dependent manner. ALA showed a higher affinity with the TE domain than PA. ALA induced breast cancer cells apoptosis, which effects were similar with the knockdown of FASN. In addition, ALA inhibited the invasion and metastasis, and arrested cell cycle in breast cancer cells. Conclusion: We propose a hypothesis that ALA could contribute to the treatment of human breast cancer by inhibiting FASN.