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

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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.

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Acknowledgments

This project was supported by Komen Foundation grant KG081632, NCI core grant CA06927, and an appropriation from the Commonwealth of Pennsylvania. We also acknowledge the use of the tissue culture facility at Fox Chase Cancer Center

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Authors and Affiliations

  1. Breast Cancer Research Laboratory, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA, 19111, USA

    Thomas J. Pogash, Ricardo López de Cicco, Maria Barton, Yanrong Su, Irma H. Russo & Jose Russo

  2. Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey Medical Center, Hershey, PA, USA

    Karam El-Bayoumy

  3. Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey Medical Center, Hershey, PA, USA

    Shantu Amin & Krishne Gowda

  4. Natural Science Department, DeSales University, Center Valley, PA, USA

    Julie A. Himmelberger

  5. Department of Biostatistics and Bioinformatics, Fox Chase Cancer Center, Philadelphia, PA, USA

    Michael Slifker

  6. Department of Medicine, Pennsylvania State University College of Medicine, Hershey Medical Center, Hershey, PA, USA

    Andrea Manni

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  1. Thomas J. Pogash
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  2. Karam El-Bayoumy
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  3. Shantu Amin
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  7. Yanrong Su
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  11. Andrea Manni
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  12. Jose Russo
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Correspondence to Thomas J. Pogash.

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Editor: T. Okamoto

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Pogash, T.J., El-Bayoumy, K., Amin, S. et al. Oxidized derivative of docosahexaenoic acid preferentially inhibit cell proliferation in triple negative over luminal breast cancer cells. In Vitro Cell.Dev.Biol.-Animal 51, 121–127 (2015). https://doi.org/10.1007/s11626-014-9822-6

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  • DOI: https://doi.org/10.1007/s11626-014-9822-6

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