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

Yanwei Li, Huan Chen, Shengsheng Yang, Guangru Xie

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    Abstract

    Aromatase P450 (P450arom) 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 P450arom expression at both mRNA and protein levels by low dose puerarin treatment in both cell lines. Besides, we found that the -410/-401 bp and -565/-559 bp 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 P450arom. To further confirm if c-jun is responsible for the P450arom 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 P450arom expression and activity. Accordingly, the suppression of P450arom expression and activity by puerarin treatment may associate with the downregulation of transcription factor AP-1 or c-jun.

    Original languageEnglish (US)
    Pages (from-to)3671-3676
    Number of pages6
    JournalFood and Chemical Toxicology
    Volume46
    Issue number12
    DOIs
    StatePublished - Dec 1 2008

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    Keywords

    • AP-1
    • Aromatase P450
    • Endometriosis
    • Pueraria lobata
    • Puerarin

    ASJC Scopus subject areas

    • Food Science
    • Toxicology

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