Isoflavone Extracts Enhance the Effect of Epidermal Growth Factor Receptor Inhibitors in NSCLC Cell Lines

Anticancer Res. 2016 Nov;36(11):5827-5833. doi: 10.21873/anticanres.11167.

Abstract

Aim: We investigated the effects of the pharmacological inhibition in vitro of epidermal growth factor receptor (EGFR) in combination with isoflavones.

Materials and methods: Four anticancer drugs (erlotinib, gefitinib, afatinib and AZD9291) were combined with soy and red clover isoflavone extracts and used in cellular proliferation assays. The antitumor activity of inhibitors alone and in combination with isoflavone extracts was compared on three non-small cell lung cancer (NSCLC) cell lines with affiant EGFR genotype: A549 (EGFR wt); H1795 (EGFR T790M); HCC827 (EGFR del E746-A750).

Results: Combined treatment with extracts significantly enhanced the antiproliferative activity of all inhibitors against these cell lines. Bioactive compounds of extracts may synergize the antitumor efficacy of the inhibitors.

Conclusion: To date, as far as we are aware, this is the first report of the combined effect of isoflavone extracts and EGFR inhibitors on human NCSLC cell growth. Sequential treatment with these drugs combined with isoflavones may represent the basis for a new therapeutic approach.

Keywords: Isoflavones; antiproliferative activity; non-small cell lung cancer; tyrosine kinase inhibitors.

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Chromatography, High Pressure Liquid
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / genetics
  • Humans
  • Isoflavones / administration & dosage
  • Isoflavones / pharmacology*
  • Lung Neoplasms / pathology*
  • Spectrophotometry, Ultraviolet

Substances

  • Antineoplastic Agents
  • Isoflavones
  • ErbB Receptors