Cyclin-dependent kinase (CDK) inhibitor olomoucine enhances gamma-irradiation-induced apoptosis and cell cycle arrest in Raji cells.
Gamma-irradiation leads to apoptosis and cell cycle arrest in eukaryotic cells. Olomoucine is a novel purine analog acting as a cyclin-dependent kinase inhibitor. The effects of olomoucine in gamma-irradiation mediated cell growth inhibition and apoptosis were studied in the Raji cell line (Burkitt's lymphoma). Gamma-irradiation caused a G2 arrest, increasing the G2/M fragment of the cells. Apoptosis by gamma-irradiation was apparent both by DNA-electrophoresis and PARP-1 cleavage. The combination of olomoucine with irradiation caused an increased G2 arrest and decreased cell survival and DNA synthesis in the non-apoptotic fraction of the remaining cells. Irradiation, as well as olomoucine and the combination of both, induced apoptosis. It seems that olomoucine delays the apoptotic process and inhibits DNA fragmentation, but it decreased survival, cell cycle progression and proliferation of irradiated cells.
Boutis
Anastasios
A
Theagenion Cancer Hospital, 3rd Department of Clinical Oncology, Al. Symeonidi Str. 2, Thessaloniki 54007, Greece. tboutis@otenet.gr
Papazisis
Konstantinos
K
Pistevou-Gompaki
Kyriaki
K
Lambropoulos
Alexandros
A
Sofroniadis
Ioannis
I
Papageorgiou
Athanasios
A
Destouni
Evangelia
E
Kortsaris
Alexandros
A
D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D016195:G2 Phase / Q000187:drug effects* / Q000528:radiation effects*; D005720:Gamma Rays; D006801:Humans; D007701:Kinetin / Q000494:pharmacology*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects
D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C090046:olomoucine; D011065:Poly(ADP-ribose) Polymerases; D018844:Cyclin-Dependent Kinases; D007701:Kinetin