Antitumor activity of DL-threo-beta-fluoroasparagine against human leukemia cells in culture and L1210 cells in DBA mice.
DL-threo-beta-Fluoroasparagine (DL-threo-beta-F-Asn) inhibited the growth of murine leukemia L1210 cells and three human leukemia cell lines in culture. Fifty % inhibiting dose values ranged between 30 and 50 microM DL-threo-beta-F-Asn. L1210 cells were not sensitive to DL-erythro-beta-fluoroasparagine, DL-threo-beta-fluoroaspartic acid, or DL-erythro-beta-fluoroaspartic acid at 300 microM, the highest dose studied. The antileukemia activity of DL-threo-beta-F-Asn was studied in further detail using the L1210 model system. Inhibition of growth in culture was prevented by L-asparagine but not by D-asparagine. Inhibition of growth of L1210 cells incubated for 40 hr in the presence of 300 microM DL-threo-beta-F-Asn was reversed after DL-threo-beta-F-Asn removal. Treatment for longer periods of time resulted in cell lysis. DL-threo-beta-F-Asn at doses of 250 mg/kg increased life span in mice bearing L1210 tumors by 60%. These results demonstrate the chemotherapeutic potential of the amino acid analogue DL-threo-beta-F-Asn.
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001216:Asparagine / Q000031:analogs & derivatives* / Q000633:toxicity; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007700:Kinetics; D007938:Leukemia / Q000473:pathology*; D007939:Leukemia L1210 / Q000473:pathology*; D051379:Mice; D013329:Structure-Activity Relationship
D000596:Amino Acids; D000970:Antineoplastic Agents; D001216:Asparagine; C023464:beta-fluoroasparagine