In vivo antitumor activity of 4-amino 4-methyl 2-pentyne 1-al, an inhibitor of aldehyde dehydrogenase.
4-amino-4-methyl-2-pentyne-1-al (AMPAL), a new irreversible inhibitor of aldehyde dehydrogenase (ALDH) has been assayed for its in vitro and in vivo antitumor activity. In vitro, AMPAL inhibits the proliferation and the ALDH activity of L1210 and RBL5 cell lines. In vivo, AMPAL significantly increases the mean survival time of mice i.p. grafted with leukemia (L1210, P815, MBL2, EL4, RBL5 cell lines) or carcinoma cells (Krebs cell line), without haematopoetic toxicity. No carcinostatic effect was observed against the P388 leukemia and the 3LL Lewis lung carcinoma. A possible relationship between the ALDH isoenzyme activity of the tumor and its sensitivity to AMPAL is discussed in the light of previous reports concerning the role of aldehydes in cell growth control.
Quemener
V
V
Groupe de Recherche en Therapeutique Anticancéreuse, CNRS (SDI), C.H.U. de Rennes, France.
Quash
G
G
Moulinoux
J P
JP
Penlap
V
V
Ripoll
H
H
Havouis
R
R
Doutheau
A
A
Goré
J
J
D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors*; D000447:Aldehydes / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002287:Carcinoma, Krebs 2 / Q000188:drug therapy*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004906:Erythrocyte Count / Q000187:drug effects; D007939:Leukemia L1210 / Q000188:drug therapy; D007941:Leukemia P388 / Q000188:drug therapy; D007942:Leukemia, Experimental / Q000188:drug therapy* / Q000201:enzymology; D007958:Leukocyte Count / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains
D000447:Aldehydes; D000970:Antineoplastic Agents; C059170:4-amino-4-methyl-2-pentyne-1-al; D000444:Aldehyde Dehydrogenase