Identification of novel genes involved in the synergistic antitumor effect of caffeine in osteosarcoma cells using cDNA macroarray.
BACKGROUND
Caffeine enhances the cytocidal effects of DNA-damaging agents. This study investigated genes involved in the synergistic effect of caffeine on osteosarcoma cells using gene-profiling analysis.


METHODS
Sensitivity to cisplatin and the synergistic effect of caffeine were evaluated in five osteosarcoma cell lines with different p53 gene status. Gene expression profiles were analyzed using cDNA macroarray and verified by real-time RT-PCR.


RESULTS
The cell lines were grouped into three types with different cytotoxic patterns. Comparison of profiling data from these groups identified twelve novel genes associated with the synergistic effect of caffeine. Real-time RT-PCR analyses verified up-regulation of two apoptosis-enhancing genes and down-regulation of two interferon-inducible genes related to the synergy of caffeine.


CONCLUSIONS
These findings provide new insights into the molecular mechanisms of the synergistic effect of caffeine related to p53 gene status in osteosarcoma, providing candidates for an assay of responsiveness to caffeine-potentiated chemotherapy for osteosarcoma.
Department of Orthopaedic Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
Sadao
S
Ii
Yoshimichi
Y
Ueda
Miyako
M
Shimazaki
Shogo
S
Katsuta
Koutarou
K
Takazawa
Yoshimitsu
Y
Kanazawa
Katsuro
K
Tomita
Hiroyuki
H
Tsuchiya
D000970:Antineoplastic Agents / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D004357:Drug Synergism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D012516:Osteosarcoma / Q000235:genetics*
D000970:Antineoplastic Agents; D002110:Caffeine; D002945:Cisplatin