title: Conjugated linoleic acid alters caveolae phospholipid fatty acid composition and decreases caveolin-1 expression in MCF-7 breast cancer cells.
abstract: Conjugated linoleic acid (CLA) refers to a group of biologically active fatty acids that exhibit anticarcinogenic properties; however, the mechanism of action remains poorly understood. Caveolae are specialized plasma membrane structures that affect many facets of cancer cell function, including growth, cell signaling, and apoptosis. Therefore, one potential mechanism could be alteration of caveolae lipid composition and function. We hypothesized that CLA can alter the lipid microenvironment of caveolae and alter expression of the major caveolae-resident protein, caveolin-1. MCF-7 human breast cancer cells were treated with a vehicle control, linoleic acid (LA), or CLA for 3 days after which total cell lysate, plasma membrane, and caveolae membrane fractions were isolated. Our findings indicate that CLA readily incorporates into caveolae (Delta9cis,11trans-18:2 being the major isomer) and maybe preferentially enriched in specific phospholipid species. Furthermore, caveolin-1 localization to caveolae after treatment with CLA was decreased relative to either control- or LA-treated cells, without changes in total cellular levels of protein relative to vehicle-control treated cells. Taken together, our results suggest that further investigation of a potential therapeutic role for CLA in modulating caveolae function in breast cancer is merited.
authors.affiliation: Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada M5S3E2.
authors.forename: Pedro S P
authors.initials: PS
authors.lastname: Huot
authors.forename: Baisakhi
authors.initials: B
authors.lastname: Sarkar
authors.forename: David W L
authors.initials: DW
authors.lastname: Ma
mesh_terms: D001943:Breast Neoplasms / Q000737:chemistry / Q000648:ultrastructure*; D021941:Caveolae / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D051242:Caveolin 1 / Q000032:analysis*; D045744:Cell Line, Tumor; D005227:Fatty Acids / Q000032:analysis*; D005260:Female; D006801:Humans; D044243:Linoleic Acids, Conjugated / Q000378:metabolism / Q000494:pharmacology*; D010743:Phospholipids / Q000032:analysis* / Q000378:metabolism
chemical_list: D051242:Caveolin 1; D005227:Fatty Acids; D044243:Linoleic Acids, Conjugated; D010743:Phospholipids