Protein tyrosine kinase inhibitor, genistein, enhances apoptosis and cell cycle arrest in K562 cells treated with gamma-irradiation

Genistein, is a natural isoflavone compound with a potent activity against protein tyrosine kinases. The leukemic cell line, K562. is a bcr/abl (Phila delphia chromosome) positive cell line that is resistant to DNA-damaging ag ents, including gamma -irradiation. Treatment with genistein increased apop tosis and promoted G2-phase arrest in the non-apoptotic population of the y -irradiated K562 cells. Irradiated cells that survived 77- h after the irra diation had a normal distribution in cell cycle, whilst genistein treatment kept cells arrested in the G2-phase, decreased the S-phase fraction and su ppressed DNA-synthesis. Taken together, our results show that genistein aug ments apoptotic cell death after gamma -irradiation in K562 cells and this result cannot be attributed to abrogation of the G2/M checkpoint. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.