Mechanism of caffeine modulation of the antitumor activity of adriamycin

doi:10.1016/0378-4274(94)03154-Y

Toxicology Letters

Volume 75, Issues 1–3, January 1995, Pages 39-49

https://doi.org/10.1016/0378-4274(94)03154-Y Get rights and content

Abstract

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.

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Research articleMechanism of caffeine modulation of the antitumor activity of adriamycin

Abstract

Int. J. Radiat. Oncol. Biol. Phys.

J. Mol. Cell. Cardiol.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Chromatogr.

J. Biol. Chem.

Mutat. Res.

J. Biol. Chem.

Biochem. Biophys. Res. Commun.

New antitumor drug with significant clinical activity

Ann. Int. Med.

The clinical evaluation of analogs-III. anthracyclines

Cancer Chemother. Pharmacol.

New antitumor antibiotics, aclacinomycins A and B

J. Antibiotics

Antitumor spectrum of a new anthracycline, (2″R)-4′-O-tetrahydropyranyl-adriamycin, and effect on the cellular immune response in mice

Jpn. J. Cancer Res.

A phase I study of 4′-epi-adriamycin, a new anthracycline anticancer agent

Jpn. J. Cancer Chemother.

Aclarubicin

Jpn. J. Cancer Chemother.

Research article
Mechanism of caffeine modulation of the antitumor activity of adriamycin