Modulation of adriamycin uptake by lonidamine in ehrlich ascites tumor cells

A. Floridi, A. Gambacurta, A. Bagnato, C. Bianchi, M. G. Paggi, B. Silvestrini, A. Caputo

Research output: Contribution to journalArticle

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Abstract

The effect of Lonidamine, 1-(2,4 dichlorobenzyl)-1-H-indazol-3-carboxylic acid, on the uptake of Adriamycin by Ehrlich ascites tumor cells has been investigated. The uptake of Adriamycin is greatly stimulated by Lonidamine and the increase depends on the energy sources of the cell. In the presence of glucose the intracellular drug content is remarkably lower than that in its absence. This difference lies in the mechanism by which Lonidamine enhances the uptake of Adriamycin. The Adriamycin efflux is via an active transport process and, in the presence of glucose, both aerobic glycolysis and oxidative phosphorylation contribute to ATP synthesis. Although Lonidamine inhibits both these pathways, there is still sufficient ATP to extrude a certain amount of Adriamycin. The elevated intracellular concentration of Adriamycin depends not only on the Lonidamine-inhibited outward transport but also on higher membrane permeability which allows a low concentration of Adriamycin (18 μM) to interfere also with the oxidative metabolism of Ehrlich ascites tumor cells.

Original languageEnglish
Pages (from-to)421-431
Number of pages11
JournalExperimental and Molecular Pathology
Volume49
Issue number3
DOIs
Publication statusPublished - 1988

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Ehrlich Tumor Carcinoma
Doxorubicin
Tumors
Cells
Modulation
Adenosine Triphosphate
Glucose
Active Biological Transport
Oxidative Phosphorylation
Glycolysis
Carboxylic Acids
lonidamine
Metabolism
Permeability
Membranes
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Pathology and Forensic Medicine

Cite this

Modulation of adriamycin uptake by lonidamine in ehrlich ascites tumor cells. / Floridi, A.; Gambacurta, A.; Bagnato, A.; Bianchi, C.; Paggi, M. G.; Silvestrini, B.; Caputo, A.

In: Experimental and Molecular Pathology, Vol. 49, No. 3, 1988, p. 421-431.

Research output: Contribution to journalArticle

Floridi, A. ; Gambacurta, A. ; Bagnato, A. ; Bianchi, C. ; Paggi, M. G. ; Silvestrini, B. ; Caputo, A. / Modulation of adriamycin uptake by lonidamine in ehrlich ascites tumor cells. In: Experimental and Molecular Pathology. 1988 ; Vol. 49, No. 3. pp. 421-431.
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abstract = "The effect of Lonidamine, 1-(2,4 dichlorobenzyl)-1-H-indazol-3-carboxylic acid, on the uptake of Adriamycin by Ehrlich ascites tumor cells has been investigated. The uptake of Adriamycin is greatly stimulated by Lonidamine and the increase depends on the energy sources of the cell. In the presence of glucose the intracellular drug content is remarkably lower than that in its absence. This difference lies in the mechanism by which Lonidamine enhances the uptake of Adriamycin. The Adriamycin efflux is via an active transport process and, in the presence of glucose, both aerobic glycolysis and oxidative phosphorylation contribute to ATP synthesis. Although Lonidamine inhibits both these pathways, there is still sufficient ATP to extrude a certain amount of Adriamycin. The elevated intracellular concentration of Adriamycin depends not only on the Lonidamine-inhibited outward transport but also on higher membrane permeability which allows a low concentration of Adriamycin (18 μM) to interfere also with the oxidative metabolism of Ehrlich ascites tumor cells.",
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