Abstract 617: Repression of cell proliferation and androgen receptor activity by 2’-hydroxyflavanone in prostate cancer cells

Abstract

Abstract Background: Since androgen-androgen receptor (AR) axis is the main stream for development and progression of prostate cancer, androgen-deprivation therapy (ADT) is conducted as a first line hormonal therapy using medical castration, such as LH-RH agonists, LH-RH antagonist, and antiandrogen for advanced PCa. After an initial response to ADT, however, PCa eventually loses responsiveness to ADT and progresses into castration-resistant prostate cancer (CRPC). Prevention of the development of castration-resistant from hormone-naïve prostate cancer is an important issue in maintaining the quality of life of the patients. We explored the effect of 2’-hydroxyflavanone on proliferation and androgen responsiveness using prostate cancer cell lines. Materials and Methods: To investigate the effect of 2’ -hydroxyflavanone on proliferation, prostate cancer cells were treated with 2’-hydroxyflavanone. Androgen-responsiveness in LNCaP cells was confirmed by luciferase assay after transfection of luciferase reporter driven by prostate specific antigen promoter. To detect androgen receptor (AR) expression, reverse transcriptase polymerase chain reaction and western blot analysis were conducted. Results: 2’ -Hydroxyflavanone inhibited the proliferation of PC-3 and DU145 cells by induction of apoptosis. 2’ -Hydroxyflavanone inhibited the proliferation of LNCaP cells stimulated by androgens and attenuated androgen-responsiveness through down-regulation of AR protein. Conclusion: 2’ -Hydroxyflavanone not only inhibited proliferation of prostate cancer cells, but also repressed androgen-responsiveness, suggesting that it might be an useful agent in preventing recurrence of prostate cancer. Citation Format: Atsushi Mizokami, Mitsuo Ofude, Misako Kumaki, Kouji Izumi, Hiroyuki Konaka, Yoshifumi Kadono, Minkyoung Shin, Jian Zhang, Evan T. Keller, Mikio Namiki. Repression of cell proliferation and androgen receptor activity by 2’-hydroxyflavanone in prostate cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 617. doi:10.1158/1538-7445.AM2014-617