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Berberine inhibits androgen synthesis by interaction with aldo-keto reductase 1c3 in 22Rv1 prostate cancer cells

Asian Journal of Andrology 2016年第4期18卷 607-612页

作者： Yuantong Tian , Lijing Zhao Ye Wang Haitao Zhang Duo Xu Xuejian Zhao Yi Li Jing Li Department of Pharmacology College of Basic Medical Science Jilin University Changchun 130021 China Gannan Medical University Ganzhou Jiangxi 341000 China School of Life Science Jilin University Changchun 130012 China Tulane cancer center Tulane University School of Medicine 1430 Tulane Avenue SL-79 New Orleans LA 70112 USA

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.

关键词： aldo-keto reductase family 1 member c3 androgen berberine castration-resistant prostate cancer

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