Observations with an S-adenosylmethionine decarboxylase inhibitor in rats with prostatic adenocarcinoma.
CGP 48664A (2-(4-aminoiminomethyl)-2,3-dihydro-1H-inden-1-ylidene dihydrochloride, CAS 149400-88-4) is a new potent inhibitor of S-adenosylmethionine decarboxylase with antitumor properties. In view of the eminent clinical problems in the treatment of non hormone dependent prostatic cancer, the antiproliferative potency of this compound was tested in Dunning MAT-LyLu rat prostatic adenocarcinoma. The compound proved inefficient in preventing the growth of this tumor, even at a near toxic dose. A reason for the lacking effect is presumably the inadequate accumulation of the drug in the tumor cells due to the excessive growth rate of the MAT-LyLu xenografts. Tumor growth seems not to be accompanied by a proportionally rapid vascularization of the tumor mass. CGP 48664A was found to be a potent inhibitor of polyamine oxidase. This property of the drug may have contributed to the activation of the phagocytic capacity of peritoneal macrophages from tumor-bearing rats.
Institut de Recherche Contre le Cancer, Université de Rennes, France.
N
N
Seiler
J G
JG
Delcros
B
B
Cipolla
L
L
Chamaillard
R
R
Havouis
V
V
Quemener
J P
JP
Moulinoux
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D012437:Adenosylmethionine Decarboxylase / Q000037:antagonists & inhibitors*; D000578:Amidines / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015317:Biogenic Polyamines / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D007189:Indans / Q000627:therapeutic use*; D008099:Liver / Q000378:metabolism; D008175:Lung Neoplasms / Q000556:secondary; D017737:Macrophages, Peritoneal / Q000187:drug effects; D008297:Male; D009368:Neoplasm Transplantation; D009929:Organ Size / Q000187:drug effects; D010587:Phagocytosis / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains
D000578:Amidines; D000970:Antineoplastic Agents; D015317:Biogenic Polyamines; D004791:Enzyme Inhibitors; D007189:Indans; C082408:4-amidinoindan-1-one 2'-amidinohydrazone; D012437:Adenosylmethionine Decarboxylase