Androprostamine A: a unique antiprostate cancer agent

• Published in: Journal of antibiotics Vol. 74; no. 10; pp. 717 - 725
• Main Authors: Yamazaki, Yohko, Abe, Hikaru, Sakashita, Chiharu, Ohba, Shun-Ichi, Watanabe, Takumi, Momose, Isao, Kawada, Manabu
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-10-2021; Nature Publishing Group
• Subjects: 38/77; 631/67/1059/99; 631/67/589/466; 82/80; Androgen receptors; Androgens; Antigens; Antineoplastic Agents - chemistry; Antineoplastic Agents - metabolism; Antineoplastic Agents - therapeutic use; Bacteriology; Biomedical and Life Sciences; Bioorganic Chemistry; Broths; Cell culture; Cell Line, Tumor; Cell Survival - drug effects; Cinnamates - chemistry; Cinnamates - metabolism; Cinnamates - therapeutic use; Cytotoxicity; Gene expression; Gene Expression Regulation, Neoplastic - drug effects; Humans; Life Sciences; Male; Medicinal Chemistry; Microbiology; Microorganisms; Molecular Structure; Oligopeptides - chemistry; Oligopeptides - metabolism; Oligopeptides - therapeutic use; Oral administration; Organic Chemistry; Prostate cancer; Prostate-specific antigen; Prostatic Neoplasms - drug therapy; Special Feature: Article; Streptomyces - metabolism; Therapeutic targets; Toxicity; Transcription
• ISSN: 0021-8820; 1881-1469
• DOI: 10.1038/s41429-021-00449-8

The androgen receptor (AR) is an important therapeutic target for all clinical states of prostate cancer. We screened cultured broths of microorganisms for their ability to suppress androgen-dependent growth of human prostate cancer LNCaP and VCaP cells without cytotoxicity. We have already identified androprostamine A (APA) from a
Streptomyces
culture broth as a functional inhibitor of AR. APA repressed R1881 (the synthetic androgen methyltrienolone)-induced androgen-regulated gene expression and dramatically inhibited R1881-induced prostate-specific antigen levels. However, APA did not act as an AR antagonist and did not inhibit AR transcriptional activity. Moreover, AS2405, an APA derivative, significantly inhibited the growth of VCaP cells in SCID mice upon oral administration.