UICC World Cancer Congress 2006

Objective:Caffeine enhances the cytocidal effects of anticancer drugs on tumor cells due to its DNA-repair inhibiting or apoptosis-inducing effect. In our previous clinical study, we demonstrated that caffeine-potentiated chemotherapy induced complete response at a high rate (83%) in patients with osteosarcoma (OS). The objective of our study was to examine caffeine-induced changes in gene expressions in human OS cells using cDNA array.

Methods:We examined the synergistic effect of caffeine by cytotoxic assay in five human OS cell lines and grouped them into three types. Two cell lines were selected from different types. OST was resistant to CDDP but cytotoxic effect was strongly enhanced in combination with caffeine. HOS was sensitive to CDDP and cytotoxic effect was moderately enhanced by caffeine. OST and HOS were exposed to CDDP for 1 hr with or without subsequent addition of caffeine for 48hrs. Expression profilings of genes in response to caffeine was examined in each cell using cDNA macroarray containing 1176 human cancer-related genes.

Results:The cDNA array analysis showed up-regulation of 8 genes and down-regulation of 4 in OST cells by subsequent addition of caffeine. Of these genes, up-regulation of GADD153 and E1AF were confirmed by real-time RT-PCR. They were known to be associated with induction of apoptosis. And down-regulation of LEU13 and IFI27 were also confirmed. They were reported to be involved in resistance to anticancer drugs.