Potent genistein derivatives as inhibitors of estrogen receptor alpha-positive breast cancer

Radharani Marik, Madhan Allu, Ravi Anchoori, Vered Stearns, Christopher B. Umbricht, Saeed Khan

Research output: Contribution to journalArticlepeer-review

Abstract

The estrogen receptor (ER) is a major target for the treatment of breast cancer cells. Genistein, a soy isoflavone, possesses a structure similar to estrogen and can both mimic and antagonize estrogen effects although at high concentrations it inhibits breast cancer cell proliferation. Hence, to enhance the anticancer activity of genistein at lower concentrations, we have synthesized seven structurally modified derivatives of genistein (MA-6, MA-8, MA-11, MA-19, MA-20, MA-21 and MA-22) based on the structural requirements for an optimal anticancer effect. Among those seven, three derivatives (MA-6, MA-8 and MA-19) showed high antiproliferative activity with IC50 levels in the range of 1-2.5 μM, i.e., at much lower concentrations range than genistein itself, in three ER-positive breast cancer cell lines (MCF-7, 21PT and T47D) studied. In our analysis, we noticed that at IC50 concentrations, the MA-6, MA-8 and MA-19 genistein derivatives induced apoptosis, inhibited ERα messenger RNA expression and increased the ratio of ERβ to ERα levels in a manner comparable to the parent compound genistein. Of note, these three modified genistein derivatives exerted their effects at concentrations 10-15 times lower than the parent compound, decreasing the likelihood of significant ERα pathway activation, which has been a concern for genistein. Hence, these compounds might play a useful role in breast cancer chemoprevention.

Original languageEnglish (US)
Pages (from-to)883-892
Number of pages10
JournalCancer Biology and Therapy
Volume11
Issue number10
DOIs
StatePublished - May 15 2011

Keywords

  • Estrogen receptor alpha related breast cancer chemoprevention
  • Estrogen receptors
  • Structurally modified genistein

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

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