Anti-tumoral activity of L and D isomers of aspartic acid beta-hydroxamate on L5178Y leukemia.
D and L isomers of aspartic acid beta-hydroxamate (respectively DAH and LAH) were compared for their in vitro and in vivo activity against the murine leukemia L5178Y and their tolerance in vivo in DBA/2 mice. DAH and LAH displayed comparable cytotoxic activity against L5178Y leukemia in vitro. Death of leukemia cells was observed at concentrations above 1.2 mM for both DAH and LAH. High concentrations of L-asparagine partially reversed the growth-inhibitory effects of DAH and LAH on L5178Y cells for concentrations of DAH and LAH lower than 0.6 mM. Intraperitoneal administration of DAH and LAH to mice showed that the LD10, LD50 and LD90 of DAH was 3- to 4-fold greater for DAH than for LAH. DAH was able to eradicate L5178Y tumors in mice without inducing toxic deaths, whereas LAH at comparable doses killed all the animals treated.
INSERM U. 218-Centre Léon Bérard, Lyon, France.
N
N
Thomasset
F
F
Hamedi-Sangsari
R
R
Tournaire
C
C
Navarro
S
S
Malley
L
L
Goetsch
J
J
Grange
J
J
Vila
D000818:Animals; D001216:Asparagine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001224:Aspartic Acid; D004354:Drug Screening Assays, Antitumor; D007536:Isomerism; D007940:Leukemia L5178 / Q000188:drug therapy*; D051379:Mice; D008811:Mice, Inbred DBA
C024848:beta-aspartylhydroxamic acid; D001224:Aspartic Acid; D001216:Asparagine