Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
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Caffeine Increases the Antitumor Effect of Cisplatin in Human Hepatocellular Carcinoma Cells
Yohei KawanoMasashi NagataTakafumi KohnoAkihiro IchimiyaTomomi IwakiriManabu OkumuraKazuhiko Arimori
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2012 Volume 35 Issue 3 Pages 400-407


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.

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© 2012 The Pharmaceutical Society of Japan
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