Antiproliferative effects of retinoids related to the cell cycle-specific inhibition of ornithine decarboxylase.
The induction of ornithine decarboxylase (ODC) during G1 phase of the cell cycle appears to be universal and essential for cell cycle progression. This induction has been demonstrated in at least 23 cell types in response to various growth stimuli. Further, specific inhibitors of ODC added to several of these cell lines resulted in inhibition of cell proliferation. The studies of the effects of retinoids to inhibit Chinese hamster ovary (CHO) cell growth indicate that the cells are blocked in G1 of cell cycle, and that there is a concentration-dependent inhibition of ODC induction. Retinoids only inhibit the induction of ODC activity when added in the first 2-3 hr of G1 progression. It is postulated that ODC induction is a requirement for G1 progression and that the antiproliferative properties of retinoids are related to the specific ability to inhibit this expression. Since retinoids do not dramatically alter the rate of protein synthesis, their ability to inhibit ODC may be related to their ability to inhibit messenger RNa synthesis for ODC.
D000818:Animals; D002262:Carboxy-Lyases / Q000096:biosynthesis*; D002453:Cell Cycle / Q000187:drug effects*; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000494:pharmacology; D004224:Diterpenes; D004789:Enzyme Activation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D006801:Humans; D007700:Kinetics; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D010053:Ovary; D011494:Protein Kinases / Q000378:metabolism; D012172:Retinaldehyde / Q000494:pharmacology*; D000084562:Retinyl Esters; D014212:Tretinoin / Q000494:pharmacology*; D014801:Vitamin A / Q000031:analogs & derivatives* / Q000494:pharmacology*
D004224:Diterpenes; D000084562:Retinyl Esters; D014801:Vitamin A; C009166:retinol acetate; D014212:Tretinoin; D000242:Cyclic AMP; D011494:Protein Kinases; D002262:Carboxy-Lyases; D009955:Ornithine Decarboxylase; D012172:Retinaldehyde