Berberine inhibits androgen synthesis by interaction with aldo-keto reductase 1C3 in 22Rv1 prostate cancer cells.
Berberine inhibits androgen synthesis by interaction with aldo-keto reductase 1C3 in 22Rv1 prostate cancer cells.
复制标题
小檗碱通过与 22Rv1 前列腺癌细胞中的醛酮还原酶 1C3 相互作用抑制雄激素合成
DOI：
10.4103/1008-682x.169997
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发表时间：
2016-07
影响因子：
2.9
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Tian Y;Zhao L;Wang Y;Zhang H;Xu D;Zhao X;Li Y;Li J
醛酮还原酶家族 1 成员 C3 最近被认为是去势抵抗性前列腺癌的潜在治疗靶点。在此，我们研究了小檗碱是否通过抑制醛酮还原酶家族 1 成员 C3 来减少雄激素合成，从而延缓去势抵抗性前列腺癌的进展。测量前列腺癌细胞中的细胞活力和细胞睾酮含量。分别通过 RT-PCR 和 Western Bolt 分析检测醛酮还原酶家族 1 成员 C3 mRNA 和蛋白水平。使用 AutoDock 工具进行计算机分析，探索了小檗碱与醛酮还原酶家族 1 成员 C3 的分子相互作用。我们发现小檗碱以剂量依赖性方式抑制 22Rv1 细胞增殖并减少细胞睾酮形成。小檗碱抑制醛酮还原酶家族 1 成员 C3 酶活性，而不影响 mRNA 和蛋白质表达。分子对接研究表明，小檗碱可以进入醛酮还原酶家族1成员C3的活性中心，与氨基酸残基Phe306和Phe311形成π-π相互作用。总之，小檗碱与醛酮还原酶家族1成员C3的结构相互作用归因于抑制醛酮还原酶家族1成员C3的酶活性，并通过减少细胞内雄激素合成来抑制22Rv1前列腺癌细胞的生长。我们的研究结果为以小檗碱为先导化合物的AKR1C3抑制剂的设计、研究和开发提供了实验基础。
Aldo-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. Aldo-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 22Rv1 cells proliferation and decreased cellular testosterone formation in a dose-dependent manner. Berberine inhibited Aldo-keto reductase family 1 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 1 member C3 enzyme activity and the inhibition of 22Rv1 prostate cancer cell growth by decreasing the intracellular androgen synthesis. Our result provides the experimental basis for the design, research, and development of AKR1C3 inhibitors using berberine as the lead compound.