Dong Yaoyao, Mao Baiping, Li Linxi, Guan Hongguo, Su Ying, Li Xiaoheng, Lian Qingquan, Huang Ping, Ge Ren-Shan
Center of Scientific Research, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
Department of Anesthesiology, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
Fitoterapia. 2016 Mar;109:132-7. doi: 10.1016/j.fitote.2015.12.014. Epub 2015 Dec 19.
Gossypol is a chemical isolated from cotton seeds. It exists as (+) or (-) enantiomer and has been tested for anticancer, abortion-inducing, and male contraception. Progesterone formed from pregnenolone by 3β-hydroxysteroid dehydrogenase 1 (HSD3B1) and estradiol from androgen by aromatase (CYP19A1) are critical for the maintenance of pregnancy or associated with some cancers. In this study we compared the potencies of (+)- and (-)-gossypol enantiomers in the inhibition of HSD3B1 and aromatase activities as well as progesterone and estradiol production in human placental JEG-3 cells. (+) Gossypol showed potent inhibition on human placental HSD3B1 with IC50 value of 2.3 μM, while (-) gossypol weakly inhibited it with IC50 over 100 μM. In contrast, (-) gossypol moderately inhibited CYP19A1 activity with IC50 of 23 μM, while (+) gossypol had no inhibition when the highest concentration (100 μM) was tested. (+) Gossypol enantiomer competitively inhibited HSD3B1 against substrate pregnenolone and showed mixed mode against NAD(+). (-) Gossypol competitively inhibited CYP19A1 against substrate testosterone. Gossypol enantiomers showed different potency related to their inhibition on human HSD3B1 and CYP19A1. Whether gossypol enantiomer is used alone or in combination relies on its application and beneficial effects.
棉酚是从棉籽中分离出的一种化学物质。它以（+）或（-）对映体形式存在，并已进行过抗癌、引产和男性避孕方面的测试。由孕烯醇酮通过3β-羟基类固醇脱氢酶1（HSD3B1）生成的孕酮以及由雄激素通过芳香化酶（CYP19A1）生成的雌二醇对于维持妊娠至关重要或与某些癌症相关。在本研究中，我们比较了（+）-和（-）-棉酚对映体在抑制人胎盘JEG-3细胞中HSD3B1和芳香化酶活性以及孕酮和雌二醇生成方面的效力。（+）棉酚对人胎盘HSD3B1表现出强效抑制作用，IC50值为2.3 μM，而（-）棉酚对其抑制作用较弱，IC50超过100 μM。相反，（-）棉酚对CYP19A1活性有中度抑制作用，IC50为23 μM，而在测试最高浓度（100 μM）时（+）棉酚无抑制作用。（+）棉酚对映体对底物孕烯醇酮竞争性抑制HSD3B1，对NAD(+)表现出混合模式。（-）棉酚对底物睾酮竞争性抑制CYP19A1。棉酚对映体在抑制人HSD3B1和CYP19A1方面表现出不同的效力。棉酚对映体单独使用还是联合使用取决于其应用和有益效果。
