Synthetic genistein glycosides inhibiting EGFR phosphorylation enhance the effect of radiation in HCT 116 colon cancer cells.
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.
Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Silesian University of Technology, Krzywoustego 4, 44-100 Gliwice, Poland. krawczyk@io.gliwice.pl.
Aleksandra
A
Gruca
Center for Translational Research and Molecular Biology of Cancer, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Wybrzeze Armii Krajowej 15, 44-100 Gliwice, Poland. krawczyk@io.gliwice.pl.
Zdzisław
Z
Krawczyk
Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Silesian University of Technology, Krzywoustego 4, 44-100 Gliwice, Poland. wieslaw.szeja@adres.pl.
Wiesław
W
Szeja
Pharmaceutical Research Institute, Rydygiera 8, 01-793 Warsaw, Poland. g.grynkiewicz@ifarm.eu.
Grzegorz
G
Grynkiewicz
Center for Translational Research and Molecular Biology of Cancer, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Wybrzeze Armii Krajowej 15, 44-100 Gliwice, Poland. arusin@io.gliwice.pl.
Aleksandra
A
Rusin
D016588:Anticarcinogenic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D066246:ErbB Receptors / Q000378:metabolism*; D019833:Genistein / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006027:Glycosides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects / Q000528:radiation effects; D011839:Radiation, Ionizing; D011838:Radiation-Sensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; D006027:Glycosides; D009363:Neoplasm Proteins; D011838:Radiation-Sensitizing Agents; D019833:Genistein; C512478:EGFR protein, human; D066246:ErbB Receptors