Excessive levels of diverse phytoestrogens can modulate steroidogenesis and cell migration of KGN human granulosa-derived tumor cells

Kamila A. Solak*, Fiona M.J. Wijnolts, Sandra M. Nijmeijer, Bas J. Blaauboer, Martin van den Berg, Majorie B.M. van Duursen

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Phytoestrogens are plant-derived estrogen-like compounds that are increasingly used for their suggested health promoting properties, even by healthy, young women. However, scientific concerns exist regarding potential adverse effects on female reproduction. In this study, naringenin (NAR), 8-prenylnaringenin (8-PN), genistein (GEN), coumestrol (COU), quercetin (QUE) and resveratrol (RSV) up-regulated steroidogenic acute regulatory protein (StaR) mRNA levels in KGN human granulosa-like tumor cells. Most of the phytoestrogens tested also increased CYP19A1 (aromatase) mRNA levels via activation of ovary-specific I.3 and II promoters. Yet, only NAR (3 and 10μM), COU (10 and 30μM) and QUE (10μM) also statistically significantly induced aromatase activity in KGN cells after 24h. 8-PN, aromatase inhibitor letrozole and estrogen receptor antagonist ICI 182,780 concentration-dependently inhibited aromatase activity with IC50 values of 8nM, 10nM and 72nM, respectively. Co-exposure with ICI 182,780 (0.1μM) statistically significantly attenuated the induction of aromatase activity by QUE and COU, but not NAR. Cell cycle status and proliferation of KGN cells were not affected by any of the phytoestrogens tested. Nonetheless, the migration of KGN cells was significantly reduced with approximately 30% by COU, RSV and QUE and 46% by GEN at 10μM, but not NAR and 8-PN. Our results indicate that phytoestrogens can affect various pathways in granulosa-like cells in vitro at concentrations that can be found in plasma upon supplement intake. This implies that phytoestrogens may interfere with ovarian function and caution is in place regarding the use of supplements with high contents of phytoestrogens.

Original languageEnglish
Pages (from-to)360-372
Number of pages13
JournalToxicology Reports
Volume1
DOIs
Publication statusPublished - 1 Jan 2014
Externally publishedYes

Keywords

  • Cell migration
  • CYP19
  • KGN cells
  • Ovarian-specific CYP19A1 promoters
  • Phytoestrogens
  • Tumor progression

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