Genistein induces apoptosis in ovarian cancer cells via different molecular pathways depending on Breast Cancer Susceptibility gene-1 (BRCA1) status

Karedath Abdul Aziz Thasni, Gopakumaran Rojini, S. Nair Rakesh, Thankappan Ratheeshkumar, Mani Shankar Babu, Gopala Srinivas, Asoke Banerji, Priya Srinivas

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

It has been reported that Breast Cancer Susceptibility gene-1 & 2 (BRCA1 & 2 are potential molecular targets for chemoprevention by isoflavone genistein (4′ 5, 7-trihydroxy isoflavone), in breast and prostate cancer cells. It is also known that BRCA1 has inhibitory activity on estrogen receptor-α and genistein's action on cells is mainly through modulation of estrogen receptor activity. The action of genistein with respect to BRCA1 status in ovarian cancer cells has not been reported so far. Therefore in this study, we analyzed the action of genistein on BRCA1 antisense blocked (AS4) and unblocked (NEO) BG-1 ovarian cancer cells. We found that genistein induced comparable cytotoxic effect in both AS4 and NEO cells, but through different pathways. We found that genistein induces caspase 8 dependent apoptotic pathway in NEO cells. Genistein inhibits estrogen receptor-α and activates BARD1 in BRCA1 blocked cells and induces estrogen receptor-β and FAS in presence of BRCA1. It can be concluded that even though there is no difference in the extent of cell death or apoptosis, the molecular mechanism of action of genistein in inducing apoptosis is different in BRCA1 blocked and unblocked cells. This could partially explain the beneficial effects of genistein in both wild type and mutated BRCA1 estrogen receptor positive tumors.

Original languageEnglish
Pages (from-to)158-164
Number of pages7
JournalEuropean Journal of Pharmacology
Volume588
Issue number2-3
DOIs
Publication statusPublished - 7 Jul 2008

Keywords

  • Apoptosis
  • BRCA1
  • Estrogen receptor
  • Genistein
  • Ovarian cancer

ASJC Scopus subject areas

  • Pharmacology

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