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 3 h with 100 mu M apigenin without (basal) or with 1 ng/ml luteinizing hormone (LH), 10 mM 8-bromoadenosine 3',5'-cyclic monophosphate (8BR), and 20 mu M of the following steroid substrates: 22R-hydroxychloesterol (22R), pregnenolone (P5), progesterone (P4), and androstenedione (D4). The medium levels of 5 alpha-androstane-3 alpha, 17 beta-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 3 beta-hydroxysteroid dehydrogenase, 17 alpha-hydroxylase/17, 20-lyase, and 17 beta-hydroxysteroid dehydrogenase 3 with IC50 values of 11.41 +/- 0.7, 8.98 +/- 0.10, and 9.37 +/- 0.07 mu M, respectively. Apigenin inhibited human 3 beta-hydroxysteroid dehydrogenase and 17 beta-hydroxysteroid dehydrogenase 3 with IC50 values of 2.17 +/- 0.04 and 131 +/- 0.09 mu M, respectively. Apigenin is a potent inhibitor of rat and human steroidogenic enzymes, being possible use for the treatment of prostate cancer. (C) 2016 Elsevier B.V. All rights reserved.