Mechanism of caffeine modulation of the antitumor activity of adriamycin
Autor: | Eiko Mochizuki, Yoshio Takino, Yasuyuki Sadzuka |
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Rok vydání: | 1995 |
Předmět: |
Male
DNA polymerase Ratón Cell Mice Inbred Strains Pharmacology Toxicology Ehrlich ascites carcinoma Mice chemistry.chemical_compound In vivo Caffeine Tumor Cells Cultured medicine Animals Carcinoma Ehrlich Tumor chemistry.chemical_classification biology Myocardium Drug Synergism Heart DNA Polymerase II DNA Neoplasm General Medicine DNA Polymerase I In vitro Neoplasm Proteins medicine.anatomical_structure Enzyme Liver Biochemistry chemistry Doxorubicin biology.protein |
Zdroj: | Toxicology Letters. 75:39-49 |
ISSN: | 0378-4274 |
DOI: | 10.1016/0378-4274(94)03154-y |
Popis: | We examined the effects of a combination of adriamycin (ADR) and caffeine on DNA and protein biosynthesis and on the activities of DNA polymerase α and β in normal and tumor tissue. The decrease in DNA and protein biosynthesis in tumor produced by caffeine combined with ADR were 2.5 and 2.4 times greater, respectively, compared with ADR alone. The combination of caffeine and ADR enhanced the decrease in DNA polymerases activities in the tumor which was induced by ADR, the decreases being 1.8 and 1.6 times greater, respectively, than that of ADR alone. In contrast, these ADR-induced changes in normal tissues were not enhanced by the combination with caffeine. The combination with caffeine had no effect on ADR concentration in normal tissues, but in the tumor, it increased the ADR concentration to 2.1 times that of ADR alone. In vitro, ADR efflux from Ehrlich ascites carcinoma cells was significantly inhibited by exposure to caffeine. These findings indicate that the effect of caffeine on ADR concentration in the cell plays an important role in the mechanism by which caffeine enhances ADR antitumor activity. |
Databáze: | OpenAIRE |
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