Some effects of inhibitors of polyamine synthesis on experimental prostatic cancer.
Difluoromethylornithine (DFMO) and methylglyoxal-bis(guanyl-hydrazone) (MGBG), inhibitors of ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AMDC), respectively, were tested in two experimental prostatic cancer models. DFMO resulted in a reduction in tumor size in both the rapidly growing R-3327 rat prostatic adenocarcinoma (30.5 +/- 15 versus 61 +/- 9.5 in control animals) and the human DU-145 adenocarcinomas (1.7 ml versus 3.3 ml in control animals) in nude mice. MGBG was tested only in the rat tumor, where it induced a reduction of 22.9 +/- 9.5 ml versus 61 +/- 9.5 in control animals in tumor size but was highly toxic. Flutamide or 9-B-D-arabinofuranosyladenine (Ara-A) proved ineffective per se in reducing tumor growth of the human DU-145 or of the R-3327-G strain, respectively, but increased the efficacy of DFMO against the DU-145 tumor had a high level of ODC which was reduced by DFMO of by Ara-A; the R-3327 tumor had a low level of ODC which was too low to be decreased by DFMO.
D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000230:Adenocarcinoma / Q000188:drug therapy*; D012437:Adenosylmethionine Decarboxylase / Q000037:antagonists & inhibitors*; D000818:Animals; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors*; D000518:Eflornithine; D006146:Guanidines / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008935:Mitoguazone / Q000627:therapeutic use*; D009952:Ornithine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines / Q000096:biosynthesis*; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D051381:Rats; D014740:Vidarabine / Q000627:therapeutic use
D006146:Guanidines; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines; C010192:9-(2-hydroxy-3-nonyl)adenine; D009952:Ornithine; D002262:Carboxy-Lyases; D012437:Adenosylmethionine Decarboxylase; D014740:Vidarabine; D000225:Adenine; D008935:Mitoguazone; D000518:Eflornithine