Deoxynortryptoquivaline: A unique antiprostate cancer agent

Abstract

The androgen receptor (AR) is a critical target in all the clinical stages of prostate cancer. To identify a new AR inhibitor, we constructed a new screening system using the androgen-dependent growth of prostate cancer cell lines as a screening indicator. We screened 50,000 culture broths of microorganisms using this screening system and found that the fermentation broth produced by a fungus inhibited androgen-dependent growth of human prostate cancer LNCaP cells without 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-dependent growth of human prostate cancer LNCaP cells. The AR competitor assay was performed, and DNT did not act as an AR antagonist. However, DNT inhibited AR-dependent transcriptional activity and AR nuclear translocation, it suggested that the suppression of AR function leads to inhibition activity against androgen-dependent growth. Materials and Methods Cell cultureHuman prostate cancer cell lines LNCaP, VCaP, and 22Rv1 were purchased from ATCC (Manassas, VA, USA). LNCaP and 22Rv1cells were grown in RPMI 1640 medium (NISSUI, Tokyo, Japan) containing 10% FBS