Affiliations 

  • 1 Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
  • 2 Department of Pharmaceutical Life Sciences, Faculty of Pharmacy, University of Malaya, 50603 Kuala Lumpur, Malaysia
  • 3 Department of Pathology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia; School of Health Sciences, International Medical University, Bukit Jalil, 57000 Kuala Lumpur, Malaysia
  • 4 Department of Surgery, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia; University of Malaya Cancer Research Institute, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
  • 5 Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia; University of Malaya Cancer Research Institute, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia. Electronic address: ivychung@ummc.edu.my
Biochimie, 2020 Dec;179:23-31.
PMID: 32931863 DOI: 10.1016/j.biochi.2020.09.005

Abstract

Different fatty acids have distinct effects on the survival of breast cancer cells, which could be mediated by fatty acid binding proteins (FABPs), a family of lipid chaperones. Due to the diverse structures of the members of FABP family, each FABP demonstrates distinct binding affinities to different fatty acids. Of note, FABP7 is predominantly expressed in triple negative breast cancer (TNBC), the most aggressive subtype of breast cancer. Yet, the role of FABP7 in modulating the effects of fatty acids on TNBC survival was unclear. In contrast to the high expression of FABP7 in human TNBC tumours, FABP7 protein was undetectable in TNBC cell lines. Hence, a FABP7 overexpression model was used for this study, in which the transduced TNBC cell lines (MDA-MB-231 and Hs578T) were treated with various mono- and polyunsaturated fatty acids. Oleic acid (OA), docosahexaenoic acid (DHA) and arachidonic acid (AA) inhibited TNBC cell growth at high concentrations, with no differences resulted from FABP7 overexpression. Interestingly, overexpression of FABP7 augmented linoleic acid-induced cell death in MDA-MB-231 cells. The increased cell death may be explained by a decrease in 13-HODE, a pro-tumorigenic oxidation product of linoleic acid. The phenotype was, however, attenuated with a rescue treatment using 25 nM 13-HODE. The decrease in 13-HODE was potentially due to fatty acid partitioning modulated by FABP7, as demonstrated by a 3-fold increase in fatty acid oxidation. Our findings suggest that linoleic acid could be a potential therapeutic strategy for FABP7-overexpressing TNBC patients.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.