Synthetic genistein glycosides inhibiting EGFR phosphorylation enhance the effect of radiation in HCT 116 colon cancer cells

Molecules. 2014 Nov 13;19(11):18558-73. doi: 10.3390/molecules191118558.


The need to find new EGFR inhibitors for use in combination with radiotherapy in the treatment of solid tumors has drawn our attention to compounds derived from genistein, a natural isoflavonoid. The antiproliferative potential of synthetic genistein derivatives used alone or in combination with ionizing radiation was evaluated in cancer cell lines using clonogenic assay. EGFR phosphorylation was assessed with western blotting. Genistein derivatives inhibited clonogenic growth of HCT 116 cancer cells additively or synergistically when used in combination with ionizing radiation, and decreased EGFR activation. Our preclinical evaluation of genistein-derived EGFR inhibitors suggests that these compounds are much more potent sensitizers of cells to radiation than the parent isoflavonoid, genistein and indicate that these compounds may be useful in the treatment of colon cancer with radiation therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticarcinogenic Agents / chemical synthesis
  • Anticarcinogenic Agents / chemistry
  • Anticarcinogenic Agents / pharmacology
  • Cell Line, Tumor
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / therapy*
  • Dose-Response Relationship, Drug
  • Dose-Response Relationship, Radiation
  • ErbB Receptors / metabolism*
  • Genistein / chemical synthesis
  • Genistein / chemistry
  • Genistein / pharmacology*
  • Glycosides / chemical synthesis
  • Glycosides / chemistry
  • Glycosides / pharmacology*
  • Humans
  • Neoplasm Proteins / metabolism*
  • Phosphorylation / drug effects
  • Phosphorylation / radiation effects
  • Radiation, Ionizing
  • Radiation-Sensitizing Agents / chemical synthesis
  • Radiation-Sensitizing Agents / chemistry
  • Radiation-Sensitizing Agents / pharmacology*


  • Anticarcinogenic Agents
  • Glycosides
  • Neoplasm Proteins
  • Radiation-Sensitizing Agents
  • Genistein
  • EGFR protein, human
  • ErbB Receptors