Berberine inhibits androgen synthesis by interaction with aldo-keto reductase 1C3 in 22Rv1 prostate cancer cells

• Published in: Asian journal of andrology Vol. 18; no. 4; pp. 607 - 612
• Main Author: Yuantong Tian , Lijing Zhao Ye Wang Haitao Zhang Duo Xu Xuejian Zhao Yi Li Jing Li
• Format: Journal Article
• Language: English
• Published: China Wolters Kluwer - Medknow Publications 01.07.2016; Medknow Publications and Media Pvt. Ltd; Medknow Publications & Media Pvt. Ltd; Medknow Publications & Media Pvt Ltd; Wolters Kluwer Medknow Publications
• Subjects: 3-Hydroxysteroid Dehydrogenases - metabolism; Aldo-Keto Reductase Family 1 Member C3; aldo-keto reductase family 1 member C3; androgen; berberine; castration-resistant prostate cancer; Androgens; Berberine; Berberine - pharmacology; Cancer cells; Cancer therapies; Care and treatment; Cell growth; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Chinese medicine; Cholesterol; Dose-Response Relationship, Drug; Enzymes; Humans; Hydroxyprostaglandin Dehydrogenases - metabolism; Male; Mortality; Nonsteroidal anti-inflammatory drugs; Original; Physiological aspects; Prostate - drug effects; Prostate - metabolism; Prostate cancer; Prostatic Neoplasms - metabolism; Proteins; RT-PCR; Studies; Testosterone; Testosterone - biosynthesis; 前列腺癌细胞; 激素合成; 盐酸小檗碱; 睾酮; 结构相互作用; 还原酶; 雄激素
• ISSN: 1008-682X; 1745-7262
• DOI: 10.4103/1008-682X.169997

AIdo-keto reductase family 1 member C3 has recently been regarded as a potential therapeutic target in castrate-resistant prostate cancer. Herein, we investigated whether berberine delayed the progression of castrate-resistant prostate cancer by reducing androgen synthesis through the inhibition of Aldo-keto reductase family 1 member C3. Cell viability and cellular testosterone content were measured in prostate cancer cells. Aido-keto reductase family 1 member C3 mRNA and protein level were detected by RT-PCR and Western bolt analyses, respectively. Computer analysis with AutoDock Tools explored the molecular interaction of berberine with Aldo-keto reductase family 1 member C3. We found that berberine inhibited 22Rvl cells proliferation and decreased cellular testosterone formation in a dose-dependent manner. Berberine inhibited Aldo-keto reductase family I member C3 enzyme activity, rather than influenced mRNA and protein expressions. Molecular docking study demonstrated that berberine could enter the active center of Aldo-keto reductase family 1 member C3 and form π-π interaction with the amino-acid residue Phe306 and Phe311. In conclusion, the structural interaction of berberine with Aldo-keto reductase family 1 member C3 is attributed to the suppression of Aldo-keto reductase family I member C3 enzyme activity and the inhibition of 22Rvl prostate cancer cell growth by decreasing the intfacellular androgen synthesis. Our result provides the experimental basis for the design, research, and development of AKRlC3 inhibitors using berberine as the lead compound.