Caffeine enhanced radiosensitivity of rat tumor cells with a mutant-type p53 by inducing apoptosis in a p53-independent manner.
The radiosensitizing effects of caffeine on two rat yolk sac tumor cell lines with a different p53 status were investigated. A reduction of radiation-induced G(2) arrest was caused by caffeine at a concentration of 2 mM in both cell lines. The reduction of survival was observed in a combination of radiation and 2 mM caffeine only in a lower radiation dose range, but not in a higher dose range in NMT-1 with a wild type p53. Radiosensitization of caffeine was recognized even in a higher dose range for cells with a mutant-type p53. Apoptosis, which was not prominent after irradiation alone or caffeine treatment alone, was induced by irradiation in combination with caffeine in cells with a mutant-type p53 through a p53-independent pathway.
Higuchi
K
K
Department of Radiology and Radiation Oncology, Gunma University School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, Japan. nmihashi@sb.gunma-u.ac.jp
Mitsuhashi
N
N
Saitoh
J
J
Maebayashi
K
K
Sakurai
H
H
Akimoto
T
T
Niibe
H
H
D000818:Animals; D017209:Apoptosis; D002110:Caffeine / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D004587:Electrophoresis, Agar Gel; D018240:Endodermal Sinus Tumor / Q000188:drug therapy / Q000532:radiotherapy; D016158:Genes, p53 / Q000235:genetics*; D015151:Immunoblotting; D009154:Mutation; D011836:Radiation Tolerance / Q000187:drug effects; D051381:Rats; D015398:Signal Transduction; D013997:Time Factors; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
C493958:Cdkn1a protein, rat; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53; D002110:Caffeine