The molecular mechanism of prostate cancer chemo-prevention agents with androgen receptor.

• Project/Area Number: 25462484
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Kyushu University
• Principal Investigator: Akira Yokomizo 九州大学, 医学(系)研究科(研究院), 准教授 (60346781)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 前立腺癌 / 化学予防 / 分子生物学

Outline of Final Research Achievements

To reveal the molecular mechanisms of chemoprevention of prostate cancer, we focused on aspirin, celecoxib and equol (isoflavone). We identified that prostaglandin receptor EP3 mediates growth inhibitory effect of aspirin through androgen receptor and contributes to castration resistance in prostate cancer cells. Furthermore, EP2 signaling mediates suppressive effects of celecoxib on androgen receptor expression and cell proliferation in prostate cancer. Finally, equol augments Skp2-mediated androgen receptor degradation. These findings will contribute to chemoprevention for prostate cancer.

Research Products

• [Journal Article] Equol inhibits prostate cancer growth via degradation of the androgen receptor by Skp2. (2016)
  • Author(s): Itsumi M, Shiota M, Takeuchi A, Kashiwagi E, Inokuchi J, Tatsugami K, Kajioka S, Uchiumi T, Naito S, Eto M, Yokomizo A.
  • Journal Title: Cancer Sci Volume: in press Pages: 327-331
  • DOI: 10.1016/j.intimp.2016.03.007
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Potential Role for YB-1 in Castration-Resistant Prostate Cancer and Resistance to Enzalutamide Through the Androgen Receptor V7. (2016)
  • Author(s): Shiota M, Fujimoto N, Imada K, Yokomizo A, Itsumi M, Takeuchi A, Kuruma H, Inokuchi J, Tatsugami K, Uchiumi T, Oda Y, Naito S.
  • Journal Title: J Natl Cancer Inst. Volume: 108 Issue: 7 Pages: djw005-djw005
  • DOI: 10.1093/jnci/djw005
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The prognostic impact of serum testosterone during androgen-deprivation therapy in patients with metastatic prostate cancer and the SRD5A2 polymorphism. (2016)
  • Author(s): Shiota M, Fujimoto N, Yokomizo A, Takeuchi A, Kashiwagi E, Dejima T, Kiyoshima K, Inokuchi J, Tatsugami K, Eto M.
  • Journal Title: Prostate Cancer Prostatic Dis. Volume: in press Issue: 2 Pages: 191-196
  • DOI: 10.1038/pcan.2016.2
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] SRD5A gene polymorphism in Japanese men predicts prognosis of metastatic prostate cancer with androgen-deprivation therapy. (2015)
  • Author(s): Shiota M, Fujimoto N, Yokomizo A, Takeuchi A, Itsumi M, Inokuchi J, Tatsugami K, Uchiumi T, Naito S.
  • Journal Title: Eur J Cancer Volume: 51 Issue: 14 Pages: 1962-9
  • DOI: 10.1016/j.ejca.2015.06.122
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] EP2 signaling mediates suppressive effects of celecoxib on androgen receptor expression and cell proliferation in prostate cancer (2014)
  • Author(s): Kashiwagi E, Shiota M, *Yokomizo A, Inokuchi J, Uchiumi T, Naito S.
  • Journal Title: Prostate Cancer P D Volume: 17 Issue: 1 Pages: 10-17
  • DOI: 10.1038/pcan.2013.53
  • Peer Reviewed / Open Access
• [Journal Article] Prostaglandin receptor EP3 mediates growth inhibitory effect of aspirin through androgen receptor and contributes to castration resistance in prostate cancer cells. (2013)
  • Author(s): Kashiwagi E, Shiota M, Yokomizo A, Itsumi M, Inokuchi J, Uchiumi T, Naito S.
  • Journal Title: Endocr Relat Cancer Volume: 20 Issue: 3 Pages: 431-441
  • DOI: 10.1530/erc-12-0344
  • Peer Reviewed
• [Presentation] Equol promotes protein degradation of androgen receptor via Skp2 and suppressed cell proliferation in prostate cancer (2015)
  • Author(s): Mmoe Itsumi, Masaki Shiota, Akira Yokomizo, Eiji Kashiwagi, Aro Takeuchi, Kenjiro Imada, Katsunori Tatsugami, Junichi Inokuchi, Takeshi Uchiumi, Shunichi Kajioka, Seiji Naito
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-10-08
  • Int'l Joint Research
• [Presentation] Isoflavons, daidzein and equol, are involved in the biology of prostate cancer (2014)
  • Author(s): Momoe Itsumi, Masaki Shiota, Akira Yokomizo, Eiji Kashiwagi, Ario Takeuchi, Keijiro Imada, Katsunori Tatsugami, Junichi Inokuchi, Takeshi Uchiumi, Seiji Naito
  • Organizer: The 4th Asian Pacific Prostate Society in Okinawa
  • Place of Presentation: 沖縄県 ブセナテラス
• [Book] Cancer, oxidative stress and dietary antioxidants (2014)
  • Author(s): Shiota M., YokomizoA., Naito S.
  • Total Pages: 283
  • Publisher: Elsevier Inc.
• [Remarks] Chapter 2 Oxidative Stress and Prostate Cancer
  • URL: http://www.sciencedirect.com/science/article/pii/B9780124052055000027