Tamoxifen and genistein synergistically down-regulate signal transduction and proliferation in estrogen receptor-negative human breast carcinoma MDA-MB-435 cells

Fei Shen, Xinjian Xue, George Weber

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

Propose. Tamoxifen and genistein were tested for synergism in estrogen receptor- negative human breast carcinoma MDA-MB-435 cells because the two compounds decrease signal transduction activity through different biochemical mechanisms and arrest the cell cycle at different phases. Materials and Methods. The combination effect of tamoxifen and genistein on signal transduction was determined by measuring IP3 concentrations and on cell proliferation and colony formation by growth inhibition assay and clonogenic assay. Results. In growth inhibition assays, for tamoxifen and genistein in the carcinoma cells the IC50s were (mean ± SE) 17 ± 0.9 and 27 ± 1.6 μM; in clonogenic assays the LC50s were 0.9 ± 0.4 and 12.5 ± 1.1 μM, respectively. When tamoxifen and genistein were simultaneously added to the cells, synergism was observed in growth inhibition, in cytotoxicity and in the reduction of inositol 1,4,5-triphosphate concentration. Conclusion. The synergistic down-regulation of signal transduction by tamoxifen and genistein may explain, in part at least, the synergistic antiproliferative and cytotoxic actions of the two compounds. The synergism of tamoxifen and genistein may be of interest in the clinical treatment of breast carcinoma.

Original languageEnglish (US)
Pages (from-to)1657-1662
Number of pages6
JournalAnticancer Research
Volume19
Issue number3 A
StatePublished - Aug 30 1999

Keywords

  • Genistein
  • Human breast carcinoma cells
  • Inositol 1,4,5-trisphosphate
  • Signal transduction
  • Synergistic down-regulation
  • Tamoxifen

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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