Screening of potential cancer-preventing chemicals for inhibition of induction of ornithine decarboxylase in epithelial cells from rat trachea.
Sixty-one selected chemicals were evaluated in rat tracheal epithelial (2C5) cells for their capacity to inhibit induction (or inhibit directly) the enzyme ornithine decarboxylase, the activity of which is associated with cell growth and division. a-Difluoromethylornithine (DFMO) was used as a positive control. At non-toxic concentrations, six test compounds had substantial activity (values for IC50 DFMO/IC50 compound >1): N-(2-carboxyphenyl)-all-trans-retinamide, ZK 119010 ¿2-(4-hydroxyphenyl)-3-methyl-1-[6-(1-pyrrolidinyl)hexyl]-1H-indol-5- ol¿, curcumin, 18-a-olean-12-ene-3 ,23,28-triol, genistein and phenethyl isothiocyanate. These should be considered for further development as cancer preventive agents.
White
E L
EL
Southern Research Institute, P.O. Box 55305, Birmingham, AL 35255-5305, USA.
Ross
L J
LJ
Schmid
S M
SM
Kelloff
G J
GJ
Steele
V E
VE
Hill
D L
DL
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002461:Cell Line, Transformed; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D000518:Eflornithine / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology*; D009955:Ornithine Decarboxylase / Q000096:biosynthesis; D065108:Ornithine Decarboxylase Inhibitors; D051381:Rats; D014132:Trachea / Q000187:drug effects / Q000201:enzymology*
D016588:Anticarcinogenic Agents; D004791:Enzyme Inhibitors; D065108:Ornithine Decarboxylase Inhibitors; D009955:Ornithine Decarboxylase; D000518:Eflornithine