Polyamine biosynthetic enzymes as targets in cancer chemotherapy.
In this chapter we focus attention on recent developments in the biosynthesis of putrescine, spermidine and spermine and their linkage to salvage pathways of methionine and adenine nucleotide synthesis. We describe the use of specific inhibitors of the polyamine biosynthetic enzymes for studying the role of polyamines in cell growth and division as well as in cell differentiation. Some novel findings are presented which suggest that part of the inhibitory action that polyamine synthesis inhibitors exert on DNA synthesis may be due to the accumulation of ADP and ATP. We show that polyamine synthesis inhibitors are capable of inducing terminal differentiation of neoplastic cells to forms with no further proliferative potential, and briefly discuss the potential use of this approach in cancer chemotherapy.
D000227:Adenine Nucleotides / Q000096:biosynthesis; D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism; D002455:Cell Division; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D004247:DNA / Q000378:metabolism; D000518:Eflornithine; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008715:Methionine / Q000096:biosynthesis; D051379:Mice; D009952:Ornithine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D011700:Putrescine / Q000096:biosynthesis*; D013095:Spermidine / Q000096:biosynthesis*; D013096:Spermine / Q000096:biosynthesis*; D013724:Teratoma / Q000378:metabolism
D000227:Adenine Nucleotides; D004791:Enzyme Inhibitors; D013096:Spermine; D004247:DNA; D008715:Methionine; D009952:Ornithine; D013095:Spermidine; D011700:Putrescine; D000518:Eflornithine