Enhanced cytotoxicity in mice of combinations of concanavalin A and selected antitumor drugs.
Concanavalin A (Con A) injected intraperitoneally at a dose of 50 mg per kg was not lethal for male BALB/c mice. Six hours after administration of 5 mg Con A/kg, the proportioy 24 hr, the proportion of granulocytes had decreased to 56%. Adiministration of 5 mg Con A/kg 24 hr before 200 mg of 5[3,3-bis(2-chloroethyl)-triazeno]-imidazole-4-carboxamide per kg, or 100 mg of 5-fluorouracil per kg resulted in a significant enhancement of lethality. Simulatenous administration of 5 mg Con A/gm and 10 mg of daunomycin per kg also resulted in enhanced lethality. Administration of 5 mg Con A/kg 24 hr before 40 mg of 1,3-bis(2-chloroethyl)-1-nitrosourea per kg, 200 mg of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea per kg, 1000 mg of cytosine arabinoside per kg, 0.1 mg of mithramycin per kg, 2 mg of pactamycin per kg or 1 mg of vincristine per kg did not result in enhanced lethality. Lipid A prepared from Escherichia coli 0127:B8 Boivin lipopolysaccharide has been complexed to Con A. The lipid A-Con A complex (5mg/kg) was no more, or less effective in enhancing the lethality of 5-fluorouracil than 2.5 mg Con A/kg. The lipid A-Con A complex (40 mg/kg), given simultaneously with drug, enhanced lethality per kg. In this regard, the lipid A-Con A complex had vincristine per kg. In this regard, the lipid A-Con A complex had activity comparable to the complex formed between lipid A and bovine serum albumin. Conceivably, Con A can be used to enhance the susceptibility of neoplastic cells to phase-specific antitumor drugs, especially those acting on deoxyribonucleic acid synthesis.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003208:Concanavalin A / Q000494:pharmacology* / Q000627:therapeutic use; D000242:Cyclic AMP; D004357:Drug Synergism; D006098:Granulocytes / Q000187:drug effects; D007958:Leukocyte Count; D008099:Liver / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy; D008288:Malaria; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000188:drug therapy; D010962:Plasmodium berghei
D000970:Antineoplastic Agents; D003208:Concanavalin A; D000242:Cyclic AMP