Effects of caffeine on neocarzinostatin-induced inhibition of cell cycle traverse in HeLa-S3 cells.

Caffeine was found to suppress the cell cycle effects of the cancer chemotherapeutic agent neocarzinostatin (NCS). When caffeine was added together with NCS to the culture of HeLa-S3 cells, NCS-induced inhibition of DNA synthesis and of mitosis was markedly reduced in the presence of caffeine. Theophylline was also effective, but N6, O2'-dibutyryl cyclic adenosine 3':5'-monophosphate was not. The caffeine-caused reduction of cell cycle effects was also observed in several other cancer chemotherapeutic agents, including bleomycin and Adriamycin. In contrast, the single-strand scission of cellular DNA and the final cell lethality induced by NCS were not affected by caffeine. These results suggest that the mechanism by which NCS inhibits the cell cycle traverse involves a kind of cell damage which is repairable in a manner promoted by caffeine and hence is different from single-strand scission of DNA. Such a mechanism might be common to the cell cycle effects of X-irradiation and several cancer chemotherapeutic agents including NCS.