Molecules, 2014, 19(11):18558-73.

Synthetic Genistein Glycosides Inhibiting EGFR Phosphorylation Enhance the Effect of Radiation in HCT 116 Colon Cancer Cells

Aleksandra Gruca, et al

Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Silesian University of Technology, Krzywoustego 4, 44-100 Gliwice, Poland； et al

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.

瑞士《分子》，2014年11月

人工合成的金雀异黄素糖苷抑制 EGFR 磷酸化，增强了辐射对 HCT 116 结肠癌细胞的影响

亚历珊德拉 格鲁克，等

波兰西里西亚科技大学有机化学，生物化学和生物技术学院等

寻找新的 EGFR 抑制剂与治疗实体肿瘤的放射治疗联合应用吸引了我们的注意力到天然异黄酮，金雀异黄素衍生的化合物。使用克隆实验对人工合成的金雀异黄素衍生物单独使用或与电离辐射联合使用的抑制肿瘤细胞增殖潜在作用进行了测试。用免疫印迹法测试了EGFR 的磷酸化。当被和电离辐射添加或协同使用时金雀异黄素衍生物抑制了 HCT 116 癌症细胞的克隆性生长并减少了 EGFR 的活性。我们对金雀异黄素派生 EGFR 抑制剂的临床前评价表明，这些化合物是更强效的增敏剂，相比与初代异黄酮，金雀异黄素，使细胞对辐射更敏感，表明这些化合物在放射治疗结肠癌中可能是有效的。