Inhibitory effect of caffeine on potentially lethal damage repair in cisplatin-treated human osteosarcoma cells.
Human osteosarcoma cells, that were cultured to confluence and maintained under low nutrient conditions, showed potentially lethal damage repair after cisplatin treatment. This repair was inhibited by a non-toxic dose of caffeine. Flow cytometric analysis indicated that cisplatin-treated cells accumulated in the S phase by 24 hr, followed by accumulation in the G2/M phase. Caffeine inhibited the initial accumulation in the S phase and the release of cells from the G2/M block. DNA synthesis was also inhibited by the cisplatin treatment. The addition of caffeine significantly reversed this inhibition. The content of DNA-bound platinum decreased over time after cisplatin treatment. Caffeine did not influence platinum content, nor did it directly affect the DNA excision repair. Cisplatin inhibits DNA synthesis in the S phase, but caffeine reduces this inhibition. Caffeine-treated cells that pass through S phase are incapable of recovery.
Yasutake
H
H
Department of Orthopaedic Surgery, School of Medicine, Kanazawa University, Japan.
Tsuchiya
H
H
Tomita
K
K
Matsunaga
T
T
Nikaido
O
O
Mori
T
T
D001859:Bone Neoplasms; D002110:Caffeine / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002945:Cisplatin / Q000633:toxicity*; D004249:DNA Damage / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D016195:G2 Phase; D006801:Humans; D007700:Kinetics; D008938:Mitosis; D012516:Osteosarcoma; D016196:S Phase; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D002110:Caffeine; D002945:Cisplatin; D013936:Thymidine