Suppression of rat and human androgen biosynthetic enzymes by apigenin: Possible use for the treatment of prostate cancer.
Apigenin is a natural flavone. It has recently been used as a chemopreventive agent. It may also have some beneficial effects to treat prostate cancer by inhibiting androgen production. The objective of the present study was to investigate the effects of apigenin on the steroidogenesis of rat immature Leydig cells and some human testosterone biosynthetic enzyme activities. Rat immature Leydig cells were incubated for 3h with 100μM apigenin without (basal) or with 1ng/ml luteinizing hormone (LH), 10mM 8-bromoadenosine 3',5'-cyclic monophosphate (8BR), and 20μM of the following steroid substrates: 22R-hydroxychloesterol (22R), pregnenolone (P5), progesterone (P4), and androstenedione (D4). The medium levels of 5α-androstane-3α, 17β-diol (DIOL), the primary androgen produced by rat immature Leydig cells, were measured. Apigenin significantly inhibited basal, 8BR, 22R, PREG, P4, and D4 stimulated DIOL production in rat immature Leydig cells. Further study showed that apigenin inhibited rat 3β-hydroxysteroid dehydrogenase, 17α-hydroxylase/17, 20-lyase, and 17β-hydroxysteroid dehydrogenase 3 with IC50 values of 11.41±0.7, 8.98±0.10, and 9.37±0.07μM, respectively. Apigenin inhibited human 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase 3 with IC50 values of 2.17±0.04 and 1.31±0.09μM, respectively. Apigenin is a potent inhibitor of rat and human steroidogenic enzymes, being possible use for the treatment of prostate cancer.
Centre of Scientific Research, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
Xiudi
X
Wang
Centre of Scientific Research, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
Guimin
G
Wang
Centre of Scientific Research, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
Xiaoheng
X
Li
Centre of Scientific Research, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
Jianpeng
J
Liu
Centre of Scientific Research, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
Tingting
T
Hong
Centre of Scientific Research, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
Qiqi
Q
Zhu
Department of Pharmacy, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China. Electronic address: huangpwly@sina.com.
Ping
P
Huang
Centre of Scientific Research, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China. Electronic address: r_ge@yahoo.com.
Ren-Shan
RS
Ge
D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D000728:Androgens / Q000096:biosynthesis*; D000818:Animals; D047310:Apigenin / Q000494:pharmacology*; D002478:Cells, Cultured; D006801:Humans; D020128:Inhibitory Concentration 50; D007985:Leydig Cells / Q000187:drug effects*; D008297:Male; D008861:Microsomes / Q000187:drug effects; D011471:Prostatic Neoplasms; D051381:Rats; D017207:Rats, Sprague-Dawley; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors*; D013737:Testis
D000728:Androgens; D047310:Apigenin; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase; D013254:Steroid 17-alpha-Hydroxylase
17α-Hydroxylase/17.20-lyase; 17β-Hydroxysteroid dehydrogenase 3; 3β-Hydroxysteroid dehydrogenase; Steroidogenesis