The Combination Effect of Caffeine and Cisplatin on a Human Lung Cancer Cell Line

It has been demonstrated that caffeine enhances the cytocidal effect of certain anticancer agents. The inhibition of DNA repair by caffeine has been considered to be one mechanism that enhances the cytocidal effect of such agents. The present study was conducted to clarify whether caffeine increases the effect of cisplatin (CDDP) on human lung adenocarcinoma cell line (PC9). CDDP concentrations used in this study were 1.0, 2.0μg/ml. After one hour treatment with CDDP, cells were washed twice with PBS and incubated in RPMI1640/10%FBS (CAF (-)) or in RPMI1640/10%FBS supplemented with 2mM caffeine (CAF (+)). Cell viability was examined by means of cell growth curves and clonogenic assay. Cell cycle analysis was performed by the two color analysis with propidium iodide (PI) and fluorescein isothiocyanate (FITC) stain using a flow cytometer (FCM). The uptakes of 3H-thymidine and 14C-leucine were measured by means of the liquid scintillation method. The results are as follows. Caffeine enhanced the cytocidal effect of CDDP at 1.0μg/ml synergisticaly. Caffeine decreased the G2M accumulation 24 hours after the CDDP exposure. Caffeine diminished fluorescence of FITC 48 hours after the CDDP exposure. The decrease of FITC fluorescence by caffeine was also observed in control. Caffeine decreased the uptake of 14C-leucine even in the control group which was not exposed to CDDP. From this data, we concluded that caffeine inhibits the protein synthesis in human lung cancer cells at a concentration which doesnot inhibit the growth of cancer cells significantly. Derangement of the protein synthesis might be the mode of caffeine-CDDP combination effect and it might give a hint as to the DNA repairing process.