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 (Philadelphia chromosome) positive cell line that is resistant to DNA-damaging agents, including gamma-irradiation. Treatment with genistein increased apoptosis and promoted G2-phase arrest in the non-apoptotic population of the gamma-irradiated K562 cells. Irradiated cells that survived 72 h after the irradiation had a normal distribution in cell cycle, whilst genistein treatment kept cells arrested in the G2-phase, decreased the S-phase fraction and suppressed DNA-synthesis. Taken together, our results show that genistein augments apoptotic cell death after gamma-irradiation in K562 cells and this result cannot be attributed to abrogation of the G2/M checkpoint.
Papazisis
K T
KT
Theagenion Cancer Hospital, 54007, Thessaloniki, Greece. paptsi@med.auth.gr
Zambouli
D
D
Kimoundri
O T
OT
Papadakis
E S
ES
Vala
V
V
Geromichalos
G D
GD
Voyatzi
S
S
Markala
D
D
Destouni
E
E
Boutis
L
L
Kortsaris
A H
AH
D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects*; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002452:Cell Count; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects*; D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D019926:Cyclin B / Q000378:metabolism; D056744:Cyclin B1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D016195:G2 Phase; D005720:Gamma Rays; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D020014:K562 Cells; D008938:Mitosis; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D013997:Time Factors; D014343:Trypan Blue
C534699:CCNB1 protein, human; C493956:CDKN1A protein, human; D019926:Cyclin B; D056744:Cyclin B1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D004247:DNA; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D016203:CDC2 Protein Kinase; D014343:Trypan Blue