title: Gossypol enantiomers potently inhibit human placental 3β-hydroxysteroid dehydrogenase 1 and aromatase activities.
abstract: 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.
authors.affiliation: Center of Scientific Research, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
authors.forename: Yaoyao
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
authors.forename: Baiping
authors.initials: B
authors.lastname: Mao
authors.affiliation: Center of Scientific Research, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
authors.forename: Linxi
authors.initials: L
authors.lastname: Li
authors.affiliation: Center of Scientific Research, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
authors.forename: Hongguo
authors.initials: H
authors.lastname: Guan
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Su
authors.affiliation: Center of Scientific Research, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
authors.forename: Xiaoheng
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
authors.forename: Qingquan
authors.initials: Q
authors.lastname: Lian
authors.affiliation: Department of Pharmacy, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China. Electronic address: huangpwly@sina.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Huang
authors.affiliation: 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. Electronic address: r_ge@yahoo.com.
authors.forename: Ren-Shan
authors.initials: RS
authors.lastname: Ge
mesh_terms: D000818:Animals; D001141:Aromatase / Q000378:metabolism; D047072:Aromatase Inhibitors / Q000494:pharmacology*; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D005260:Female; D006072:Gossypol / Q000494:pharmacology*; D006801:Humans; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors*; D010920:Placenta / Q000187:drug effects / Q000201:enzymology; D011247:Pregnancy; D011284:Pregnenolone / Q000494:pharmacology; D011375:Progesterone Reductase / Q000037:antagonists & inhibitors*; D013251:Steroid Isomerases / Q000037:antagonists & inhibitors*; D013739:Testosterone / Q000494:pharmacology
chemical_list: C021425:3 beta-hydroxysteroid oxidoreductase-delta(5) 3-ketosteroid isomerase; D047072:Aromatase Inhibitors; D009097:Multienzyme Complexes; D013739:Testosterone; D011284:Pregnenolone; D011375:Progesterone Reductase; D001141:Aromatase; C561410:CYP19A1 protein, human; D013251:Steroid Isomerases; D006072:Gossypol
keywords: 3β-hydroxysteroid dehydrogenase 1; Aromatase; Competitive inhibition; JEG-3 cells; Steroids; Testosterone