Decreased expression of aromatase in the Ishikawa and RL95-2 cells by the isoflavone, puerarin, is associated with inhibition of c-jun expression and AP-1 activity.
Aromatase P450 (P450(arom)) is overexpressed in endometriosis, endometrial cancers and uterine fibroids. With weak estrogen agonists/antagonists and some other enzymatic activities, isoflavones are increasingly advocated as a natural alternative to estrogen replacement therapy (ERT) and are available as dietary supplements. Puerarin is major isoflavonoid compound isolated from Pueraria lobata, a Chinese medicine known as Gegen. Our clinical study shows that puerarin can be used in the treatment of endometriosis, which improves pain and infertility. Assuming that the effect of puerarin on endometriosis may result from the regulation of aromatase expression or activity, we carried out this study to test the effects of puerarin on aromatase in Ishikawa and RL95-2 cell lines. Our data have demonstrated a significant decrease of P450(arom) expression at both mRNA and protein levels by low dose puerarin treatment in both cell lines. Besides, we found that the -410/-401bp and -565/-559bp regions of aromatase promoter II contained the critical cis-acting elements, binding AP-1 and c-jun. We also found that puerarin exerted a time-course effect on the inhibition of c-jun mRNA, which parallelled that of P450(arom). To further confirm if c-jun is responsible for the P450(arom) regulation by puerarin, we knocked down c-jun expression using siRNA and it indicates that c-jun acts as a considerable transcription factor in regulating P450(arom) expression and activity. Accordingly, the suppression of P450(arom) expression and activity by puerarin treatment may associate with the downregulation of transcription factor AP-1 or c-jun.
Yu
Chaoqin
C
Cancer Hospital of Tianjin, Tianjin Medical University, Ti-Yuan-Bei, Tianjin 330060, China. liyanwei127@hotmail.com
Li
Yanwei
Y
Chen
Huan
H
Yang
Shengsheng
S
Xie
Guangru
G
D024506:5' Flanking Region; D001141:Aromatase / Q000096:biosynthesis* / Q000235:genetics; D047072:Aromatase Inhibitors; D015153:Blotting, Western; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects; D004717:Endometrium / Q000166:cytology / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis*; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018808:Transcription Factor AP-1 / Q000096:biosynthesis*; D014162:Transfection
D047072:Aromatase Inhibitors; D007529:Isoflavones; D016755:Proto-Oncogene Proteins c-jun; D034741:RNA, Small Interfering; D018808:Transcription Factor AP-1; D004958:Estradiol; D012313:RNA; D008156:Luciferases; D001141:Aromatase; C033607:puerarin