The androgen receptor (AR) is a critical target in all the clinical stages of prostate cancer. To identify a new ARinhibitor, we constructed a new screening system using the androgen-dependent growth of prostate cance...The androgen receptor (AR) is a critical target in all the clinical stages of prostate cancer. To identify a new ARinhibitor, we constructed a new screening system using the androgen-dependent growth of prostate cancer cell lines as ascreening indicator. We screened 50,000 culture broths of microorganisms using this screening system and found that thefermentation broth produced by a fungus inhibited androgen-dependent growth of human prostate cancer LNCaP cellswithout cytotoxicity. Purification of this culture medium was performed, and this resulted in deoxynortryptoquivaline(DNT) being identified as a novel inhibitor of AR function. DNT showed potent inhibition of androgen-dependentgrowth of human prostate cancer LNCaP cells. The AR competitor assay was performed, and DNT did not act as anAR antagonist. However, DNT inhibited AR-dependent transcriptional activity and AR nuclear translocation, itsuggested that the suppression of AR function leads to inhibition activity against androgen-dependent growth.展开更多
基金supported by JSPS KAKENHI Grant Number JP24592417.
文摘The androgen receptor (AR) is a critical target in all the clinical stages of prostate cancer. To identify a new ARinhibitor, we constructed a new screening system using the androgen-dependent growth of prostate cancer cell lines as ascreening indicator. We screened 50,000 culture broths of microorganisms using this screening system and found that thefermentation broth produced by a fungus inhibited androgen-dependent growth of human prostate cancer LNCaP cellswithout cytotoxicity. Purification of this culture medium was performed, and this resulted in deoxynortryptoquivaline(DNT) being identified as a novel inhibitor of AR function. DNT showed potent inhibition of androgen-dependentgrowth of human prostate cancer LNCaP cells. The AR competitor assay was performed, and DNT did not act as anAR antagonist. However, DNT inhibited AR-dependent transcriptional activity and AR nuclear translocation, itsuggested that the suppression of AR function leads to inhibition activity against androgen-dependent growth.
