Oxidized derivative of docosahexaenoic acid preferentially inhibit cell proliferation in triple negative over luminal breast cancer cells

• Published in: In vitro cellular & developmental biology. Animal Vol. 51; no. 2; pp. 121 - 127
• Main Authors: Pogash, Thomas J, El-Bayoumy, Karam, Amin, Shantu, Gowda, Krishne, de Cicco, Ricardo López, Barton, Maria, Su, Yanrong, Russo, Irma H, Himmelberger, Julie A, Slifker, Michael, Manni, Andrea, Russo, Jose
• Format: Journal Article
• Language: English
• Published: Boston Springer-Verlag 01.02.2015; Springer Science & Business Media LLC; Springer US; Society for In Vitro Biology
• Subjects: Animal Genetics and Genomics; anticarcinogenic activity; Antineoplastic Agents - pharmacology; apoptosis; Biomedical and Life Sciences; breast neoplasms; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; CELL AND TISSUE MODELS; Cell Biology; Cell Culture; Cell Line, Tumor - drug effects; cell proliferation; Cell Proliferation - drug effects; Developmental Biology; docosahexaenoic acid; Docosahexaenoic Acids - metabolism; Docosahexaenoic Acids - pharmacology; Fatty Acids, Unsaturated - pharmacology; Female; Humans; Life Sciences; MCF-7 Cells - drug effects; metabolites; omega-3 fatty acids; Oxidation-Reduction; Stem Cells; tetrazolium; Triple Negative Breast Neoplasms - drug therapy; Triple Negative Breast Neoplasms - pathology; DHA; Fish oil; Triple-negative breast cancer
• ISSN: 1071-2690; 1543-706X
• DOI: 10.1007/s11626-014-9822-6

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.