title: Oxidized derivative of docosahexaenoic acid preferentially inhibit cell proliferation in triple negative over luminal breast cancer cells.
abstract: Omega-3 polyunsaturated fatty acids (PUFAs) exert an anticancer effect by affecting multiple cellular mechanisms leading to inhibition of proliferation and induction of apoptosis. It is well known that breast cancer comprises distinct molecular subtypes which differ in their responsiveness to therapeutic and preventive agents. We tested the hypothesis that n-3FA may preferentially affect triple-negative breast cancer cells for which no targeted intervention is presently available. The in vitro antiproliferative effects of n-3 PUFA docosahexaenoic acid (DHA) and its metabolite, 4-OH-DHA as well as its putative metabolite 4-OXO-DHA, were tested in five triple-negative human basal breast cell lines at different stages of transformation (MCF-10F, trMCF, bsMCF, MDA-MB-231, and BT-549) and three luminal breast cancer cell lines (MCF-7, T-47D, and SK-BR-3). Cell proliferation was measured with the tetrazolium MTT (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) assay. DHA and its oxidized derivatives significantly inhibited cell proliferation (20-90% reduction) of both basal and luminal breast cancer cell lines. The inhibitory effect was more pronounced on triple-negative basal breast cancer cell lines as compared to luminal breast cancer cell lines after 4-OXO-DHA treatment. Our data provide novel information regarding the preferential antitumor effect of oxidized derivatives of DHA on basal type breast cancer.
authors.affiliation: Breast Cancer Research Laboratory, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA, 19111, USA, Thomas.Pogash@fccc.edu.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Pogash
authors.forename: Karam
authors.initials: K
authors.lastname: El-Bayoumy
authors.forename: Shantu
authors.initials: S
authors.lastname: Amin
authors.forename: Krishne
authors.initials: K
authors.lastname: Gowda
authors.forename: Ricardo López
authors.initials: RL
authors.lastname: de Cicco
authors.forename: Maria
authors.initials: M
authors.lastname: Barton
authors.forename: Yanrong
authors.initials: Y
authors.lastname: Su
authors.forename: Irma H
authors.initials: IH
authors.lastname: Russo
authors.forename: Julie A
authors.initials: JA
authors.lastname: Himmelberger
authors.forename: Michael
authors.initials: M
authors.lastname: Slifker
authors.forename: Andrea
authors.initials: A
authors.lastname: Manni
authors.forename: Jose
authors.initials: J
authors.lastname: Russo
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000378:metabolism / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D005260:Female; D006801:Humans; D061986:MCF-7 Cells / Q000187:drug effects; D010084:Oxidation-Reduction; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy / Q000473:pathology
chemical_list: C526920:4-hydroxy-5,7,10,13,16,19-docosahexaenoic acid; C000607167:4-oxo-5,7,10,13,16,19-docosahexaenoic acid; D000970:Antineoplastic Agents; D005231:Fatty Acids, Unsaturated; D004281:Docosahexaenoic Acids