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 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.
Seiler
N
N
Merrell Dow Research Institute, Strasbourg, France.
Sarhan
S
S
Grauffel
C
C
Jones
R
R
Knödgen
B
B
Moulinoux
J P
JP
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D000518:Eflornithine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D005260:Female; D007958:Leukocyte Count / Q000187:drug effects; D008175:Lung Neoplasms / Q000178:diet therapy / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines / Q000378:metabolism*; D011700:Putrescine / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines; C044445:MDL 72527; C060377:2-(fluoromethyl)dehydroornithine ethyl ester; D011700:Putrescine; D000518:Eflornithine