Endogenous and exogenous polyamines in support of tumor growth

The combination of inhibitors of ornithine decarboxylase and polyamine oxidase and of antibiotics suitable for the (partial) decontamination of the gastrointestinal tract with a polyamine-deficient diet reduced the growth rate of Lewis lung carcinoma by more than 80%. The formation of lung metastase...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1990-08, Vol.50 (16), p.5077-5083
Main Authors: SEILER, N, SARHAN, S, GRAUFFEL, C, JONES R, KNOÊDGEN, B, MOULINOUX, J.-P
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Antineoplastic Agents - therapeutic use
Biological and medical sciences
carcinoma
Cell Division - drug effects
Chemotherapy
Eflornithine - analogs & derivatives
Eflornithine - therapeutic use
Female
Leukocyte Count - drug effects
lung
Lung Neoplasms - diet therapy
Lung Neoplasms - drug therapy
Lung Neoplasms - metabolism
Lung Neoplasms - pathology
Medical sciences
Mice
Mice, Inbred C57BL
Neoplasm Metastasis
Ornithine Decarboxylase Inhibitors
Pharmacology. Drug treatments
polyamines
Polyamines - metabolism
Putrescine - analogs & derivatives
Putrescine - therapeutic use
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Summary:The combination of inhibitors of ornithine decarboxylase and polyamine oxidase and of antibiotics suitable for the (partial) decontamination of the gastrointestinal tract with a polyamine-deficient diet reduced the growth rate of Lewis lung carcinoma by more than 80%. The formation of lung metastases was prevented by 70 to 100%, depending on the treatment. The reduction of tumor growth was accompanied by a decrease of tissue polyamine concentrations, a reduced rate of tumor cell proliferation, and protein synthesis. The comparison of the ornithine decarboxylase inhibitors Eflornithine [D,L-2-(difluoromethyl)ornithine] and (E)-2-(fluoromethyl)dehydroornithine ethylester confirmed the greater in vivo potency of the latter compound. Our method of growth inhibition by systematic polyamine deprivation is not tumor specific, but presumably generally applicable to rapid growth.
ISSN:0008-5472
1538-7445