title: Caffeine increases the antitumor effect of Cisplatin in human hepatocellular carcinoma cells.
abstract: Caffeine is thought to increase the antitumor effect of cisplatin or DNA-damaging agents because it is known that caffeine inhibits DNA repair. Caffeine-assisted chemotherapy has been used in the treatment of osteosarcomas. In addition, there are several reports about combination chemotherapy with caffeine for certain malignancies other than osteosarcomas. However, there are no reports that show the utility of combination chemotherapy with caffeine for hepatocellular carcinoma (HCC). We examined the combined effects of caffeine and cisplatin in human HCC cell lines, and screened for a more effective administration method of caffeine in vitro. Human HCC cell lines (HepG2, HLF, HuH-7, and Li-7) were exposed to caffeine (0-0.5 mM) and cisplatin (0-1.2 μg/mL) for 72 h, either alone or in combination. Cell numbers were measured by WST-8 assay, and cell apoptosis was determined by annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) binding assay. As a result, caffeine increased the antitumor effect of cisplatin on cell proliferation and cell apoptosis in the HCC cell lines. Moreover, this effect was dependent on the amount of exposure to caffeine. These results suggest that caffeine-assisted chemotherapy is useful for HCC treatment.
authors.affiliation: Department of Pharmacy, University of Miyazaki Hospital, Kiyotake-cho, Miyazaki, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Kawano
authors.forename: Masashi
authors.initials: M
authors.lastname: Nagata
authors.forename: Takafumi
authors.initials: T
authors.lastname: Kohno
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ichimiya
authors.forename: Tomomi
authors.initials: T
authors.lastname: Iwakiri
authors.forename: Manabu
authors.initials: M
authors.lastname: Okumura
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Arimori
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002110:Caffeine / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002945:Cisplatin / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D006801:Humans
chemical_list: D000970:Antineoplastic Agents; D002110:Caffeine; D002945:Cisplatin