Effects of Methylxanthine Derivatives on Adriamycin Concentration and Antitumor Activity

We studied the mechanism whereby caffeine acts as a biochemical modulator of adriamycin, and examined various methylxanthine derivatives to determine whether they would be of value as biochemical modulators. In an in vitro study of adriamycin efflux in Ehrlich ascites carcinoma cells, theophylline,...

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Published in:Cancer science 1995-06, Vol.86 (6), p.594-599
Main Authors: Sadzuka, Yasuyuki, Iwazaki, Ayano, Miyagishima, Atsuo, Nozawa, Yasuo, Hirota, Sadao
Format: Article
Language:English
Subjects:
Adriamycin
Adriamycin efflux
Animals
Antineoplastic agents
Antitumor activity
Ascites
Biochemical modulation
Biological and medical sciences
Caffeine
Caffeine - pharmacology
Carcinoma, Ehrlich Tumor - drug therapy
Carcinoma, Ehrlich Tumor - metabolism
Carcinoma, Ehrlich Tumor - mortality
Doxorubicin - metabolism
Doxorubicin - pharmacology
Drug Synergism
General aspects
Male
Medical sciences
Metabolites
Mice
Pentoxifylline - pharmacology
Pharmacology. Drug treatments
Theobromine
Theobromine - pharmacology
Theophylline
Theophylline - pharmacology
Tumors
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description We studied the mechanism whereby caffeine acts as a biochemical modulator of adriamycin, and examined various methylxanthine derivatives to determine whether they would be of value as biochemical modulators. In an in vitro study of adriamycin efflux in Ehrlich ascites carcinoma cells, theophylline, pentoxifylline, and theobromine inhibited this efflux, while caffeine metabolites did not. The effects of several methylxanthine derivatives on the antitumor activity of adriamycin and on adriamycin concentration in tissue were also examined in CDF1 tumor‐bearing mice. Theobromine, which inhibited adriamycin efflux in vitro, increased the antitumor activity of adriamycin and the concentration of adriamycin in tumors. The caffeine metabolites, which had no effect on the adriamycin efflux, did not increase antitumor activity. These results suggest that the metabolism of caffeine may weaken its effect as a biochemical modulator, and that pentoxifylline and theobromine would be of value as biochemical modulators of adriamycin.
doi_str_mv 10.1111/j.1349-7006.1995.tb02439.x
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identifier ISSN: 0910-5050
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source Publicly Available Content Database (Proquest) (PQ_SDU_P3); PubMed Central
subjects Adriamycin
Adriamycin efflux
Animals
Antineoplastic agents
Antitumor activity
Ascites
Biochemical modulation
Biological and medical sciences
Caffeine
Caffeine - pharmacology
Carcinoma, Ehrlich Tumor - drug therapy
Carcinoma, Ehrlich Tumor - metabolism
Carcinoma, Ehrlich Tumor - mortality
Doxorubicin - metabolism
Doxorubicin - pharmacology
Drug Synergism
General aspects
Male
Medical sciences
Metabolites
Mice
Pentoxifylline - pharmacology
Pharmacology. Drug treatments
Theobromine
Theobromine - pharmacology
Theophylline
Theophylline - pharmacology
Tumors
title Effects of Methylxanthine Derivatives on Adriamycin Concentration and Antitumor Activity
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