The Curcumin Derivative, H10, Suppresses Hormone-Dependent Prostate Cancer by Inhibiting 17β-Hydroxysteroid Dehydrogenase Type 3
The Curcumin Derivative, H10, Suppresses Hormone-Dependent Prostate Cancer by Inhibiting 17β-Hydroxysteroid Dehydrogenase Type 3
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DOI：
10.3389/fphar.2020.00637
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发表时间：
2020-05-08
影响因子：
5.6
通讯作者：
Xiang, Qi
中科院分区：
文献类型：
--
作者：
Cheng, Yating;Yang, Yan;Xiang, Qi
17 β -羟基类固醇脱氢酶3型（17 β - hsd3）酶是激素依赖性前列腺癌的潜在治疗靶点，因为它是睾酮(T)生物合成最后一步的关键酶。姜黄素类似物H10在稳定过表达17 β - hsd3酶（LC540 [17 β - hsd3]）的LC540细胞中抑制T的产生（P < 0.01），而不影响黄体酮(P)的合成。在10、20和40 μ M剂量下，H10将含有17 β - hsd3酶的大鼠睾丸微粒体部分T的产量分别从100下调至78.41 +/- 7.41%、51.86 +/- 10.03%和45.14 +/- 8.49%。参与17 β - hsd3介导的雄激素向T转化的17 β - hsd3、3 β - HSD1、CYP17a1、CYP11a1、STAR蛋白表达量各组间差异无统计学意义（P < 0.05）。这表明H10在体外仅抑制17 β - hsd3的酶活性。此外，H10还能抑制LNCaP细胞在体内的异种移植物生长。我们得出结论，H10可以作为17 β - hsd3的有效抑制剂，从而抑制雄激素的生物合成和前列腺癌的进展。
The 17 beta-hydroxysteroid dehydrogenase type 3 (17 beta-HSD3) enzyme is a potential therapeutic target for hormone-dependent prostate cancer, as it is the key enzyme in the last step of testosterone (T) biosynthesis. A curcumin analog, H10, was optimized for inhibiting T production in LC540 cells that stably overexpressed 17 beta-HSD3 enzyme (LC540 [17 beta-HSD3]) (P < 0.01), without affecting progesterone (P) synthesis. H10 downregulated the production of T in the microsomal fraction of rat testes containing the 17 beta-HSD3 enzyme from 100 to 78.41 +/- 7.41%, 51.86 +/- 10.03%, and 45.14 +/- 8.49% at doses of 10, 20, and 40 mu M, respectively. There were no significant differences among the groups with respect to the protein expression levels of 17 beta-HSD3, 3 beta HSD1, CYP17a1, CYP11a1, and STAR, which participate in 17 beta-HSD3-mediated conversion of androgens to T (P > 0.05). This indicated that H10 only inhibited the enzymatic activity of 17 beta-HSD3 in vitro. Furthermore, H10 inhibited the adione-stimulated growth of xenografts established from LNCaP cells in nude mice in vivo. We conclude that H10 could serve as an effective inhibitor of 17 beta-HSD3, which in turn would inhibit the biosynthesis of androgens and progression of prostate cancer.