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Research Article

Genistein Prevents Development of Spontaneous Ovarian Cancer and inhibits Tumor Growth in Hen Model

Kazim Sahin, Engin Yenice, Birdal Bilir, Cemal Orhan, Mehmet Tuzcu, Nurhan Sahin, Ibrahim H. Ozercan, Nashwa Kabil, Bulent Ozpolat and Omer Kucuk
Kazim Sahin
Department of Animal Nutrition, Faculty of Veterinary Medicine, Firat University
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Engin Yenice
animal nutrition, Poultry Researach institute
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Birdal Bilir
Hematology and Medical Oncology, Emory University School of Medicine
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Cemal Orhan
Department of Animal Nutrition, Faculty of Veterinary Medicine, Firat University
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  • ORCID record for Cemal Orhan
Mehmet Tuzcu
Department of Biology, Firat University
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Nurhan Sahin
Department of Animal Nutrition, Faculty of Veterinary Medicine, Firat University
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Ibrahim H. Ozercan
Department of Pathology, Faculty of Medicine, Firat University
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Nashwa Kabil
Department of Experimental Therapeutics, University of Texas M.D. Anderson Cancer Center
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Bulent Ozpolat
Experimental Therapeutics, University of Texas MD Anderson Cancer Center
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  • For correspondence: bozpolat@mdanderson.org
Omer Kucuk
Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine
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DOI: 10.1158/1940-6207.CAPR-17-0289
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Abstract

Genistein, the major isoflavone in soybean, has been reported to exert anticancer effects on various types of cancer including ovarian cancer; however, its chemopreventive effects and mechanisms of action in ovarian cancer have not been fully elucidated in spontaneously developing ovarian cancer models. In the present study, we demonstrated the preventive effects and mechanisms of genistein in the laying hen model that develops spontaneous ovarian cancer at high incidence rates. Laying hens were randomized to three groups: control (3.01 mg/hen, n = 100) or low (52.48 mg/hen n=100) and high genistein supplementation (106.26 mg/hen per day; per group). At the end of 78 weeks, hens were euthanized and ovarian tumors were collected and analyzed. We observed that genistein supplementation significantly reduced the ovarian tumor incidence (p = 0.002) as well as the number and size of the tumors (p= 0.0001). Molecular analysis of the ovarian tumors revealed that genistein downregulated serum malondialdehyde (MDA), a marker for oxidative stress and the expression of NF-κB, Bcl-2 and whereas it upregulated Nrf2, HO-1 and Bax expression at protein level in ovarian tissues. Moreover, genistein intake decreased the activity of mTOR pathway as evidenced by reduced phosphorylation of mTOR, p70S6K1, and 4E-BP1. Taken together, our findings strongly support the potential of genistein in the chemoprevention of ovarian cancer and highlight the effects of the genistein on the molecular pathways involved in ovarian tumorigenesis.

  • Received September 8, 2017.
  • Revision received July 30, 2018.
  • Accepted January 10, 2019.
  • Copyright ©2019, American Association for Cancer Research.

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Published OnlineFirst January 16, 2019
doi: 10.1158/1940-6207.CAPR-17-0289

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Genistein Prevents Development of Spontaneous Ovarian Cancer and inhibits Tumor Growth in Hen Model
Kazim Sahin, Engin Yenice, Birdal Bilir, Cemal Orhan, Mehmet Tuzcu, Nurhan Sahin, Ibrahim H. Ozercan, Nashwa Kabil, Bulent Ozpolat and Omer Kucuk
Cancer Prev Res January 16 2019 DOI: 10.1158/1940-6207.CAPR-17-0289

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Genistein Prevents Development of Spontaneous Ovarian Cancer and inhibits Tumor Growth in Hen Model
Kazim Sahin, Engin Yenice, Birdal Bilir, Cemal Orhan, Mehmet Tuzcu, Nurhan Sahin, Ibrahim H. Ozercan, Nashwa Kabil, Bulent Ozpolat and Omer Kucuk
Cancer Prev Res January 16 2019 DOI: 10.1158/1940-6207.CAPR-17-0289
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Cancer Prevention Research
eISSN: 1940-6215
ISSN: 1940-6207

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