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Oncol Lett. 2017 Jan;13(1):243-249. doi: 10.3892/ol.2016.5382. Epub 2016 Nov 11.

DHA blocks TPA-induced cell invasion by inhibiting MMP-9 expression via suppression of the PPAR-γ/NF-κB pathway in MCF-7 cells.

Author information

1
Center for Metabolic Function Regulation, Wonkwang University School of Medicine, Iksan, Jeonbuk 570-749, Republic of Korea.
2
Department of Oncology Medicine, Xinhua Hospital Affiliated to Dalian University, Dalian, Liaoning 116021, P.R. China.
3
Department of Biochemistry, Institute of Medical Science, Chonbuk National University Medical School, Jeonju, Jeonbuk 560-182, Republic of Korea.
4
Department of Surgery, Division of Breast Thyroid Surgery, Chonbuk National University Medical School, Jeonju, Jeonbuk 560-182, Republic of Korea.
5
Center for Metabolic Function Regulation, Wonkwang University School of Medicine, Iksan, Jeonbuk 570-749, Republic of Korea; Department of Korean Physiology, School of Korean Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.
6
Center for Metabolic Function Regulation, Wonkwang University School of Medicine, Iksan, Jeonbuk 570-749, Republic of Korea; Department of Oral Biochemistry, Institute of Biomaterials Implant, School of Dentistry, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.

Abstract

Docosahexaenoic acid (DHA) is an omega-3 fatty acid that is considered to have applications in cancer prevention and treatment. The beneficial effects of DHA against cancer metastasis are well established; however, the mechanisms underlying these effects in breast cancer are not clear. Cell invasion is critical for neoplastic metastasis, and involves the degradation of the extracellular matrix by matrix metalloproteinase (MMP)-9. The present study investigated the inhibitory effect of DHA on MMP-9 expression and cell invasion induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in the MCF-7 breast cancer cell line. DHA inhibited the TPA-induced activation of mitogen-activated protein kinase (MAPK) and the transcription of nuclear factor (NF)-κB, but did not inhibit the transcription of activator protein-1. DHA increased the activity of peroxisome proliferator-activated receptor (PPAR)-γ, an effect that was reversed by the application of the PPAR-γ antagonist GW9662. In addition, combined treatment with GW9662 and DHA increased NF-κB-related protein expression. These results indicate that DHA regulates MMP-9 expression and cell invasion via modulation of the MAPK signaling pathway and PPAR-γ/NF-κB activity. This suggests that DHA could be a potential therapeutic agent for the prevention of breast cancer metastasis.

KEYWORDS:

DHA; MCF-7; MMP-9; NF-κB; PPAR-γ; invasion

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