Combined effects of synthetic lipid A analogs and muramyl dipeptide on antitumor activity against Meth A fibrosarcoma in mice.
Combined effects of chemically synthesized lipid A analogs, the compound A-171 (acylglucosamine-4-phosphate with (R)-3-hydroxytetradecanoyl and (R)-3-hydroxytetradecanoyloxy]tetradecanoyl group at the C-2 and C-3 positions), or the compound A-172 (with (R)-3-hydroxytetradecanoyloxy]tetradecanoyl and (R)-3-tetradecanoyloxytetradecanoyl group at the C-2 and C-3 positions), and muramyl dipeptide (MDP) on antitumor activity against Meth A fibrosarcoma, were examined. Meth A fibrosarcoma cells (5 X 10(5)) were inoculated intradermally into BALB/c mice on day 0, compound A-172 and/or MDP were administered intravenously (i.v.) on day 7. Although the antitumor activity by single i.v. injection of A-172 (50 micrograms/mouse) with MDP (10 micrograms) was weaker than that of 50 micrograms of synthetic lipid A analogs (506), or 10 micrograms of bacterial lipopolysaccharide (LPS) with MDP, A-172 alone and with MDP exhibited tumor inhibition rates of 49.0 and 70.6%, respectively. When A-171 (50 micrograms) with MDP (10 micrograms) was administered i.v. twice (days 7 and 10) into mice inoculated Meth A fibrosarcoma, two of five mice caused complete tumor regression. Furthermore, L929 cell lysis by the combination of A-171, A-172 with MDP was higher than that by the analogs or MDP alone, suggesting that the lipid A analogs of monosaccharide type as well as LPS are able to enhance the production of tumor necrosis factor in the presence of MDP.
Shimizu
T
T
Department of Microbiology, University of Shizuoka, School of Pharmaceutical Sciences, Japan.
Ohtsuka
Y
Y
Yanagihara
Y
Y
Itoh
H
H
Nakamoto
S
S
Achiwa
K
K
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology*; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005354:Fibrosarcoma / Q000188:drug therapy*; D007271:Injections, Intradermal; D008050:Lipid A / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D014407:Tumor Cells, Cultured
D008050:Lipid A; D000119:Acetylmuramyl-Alanyl-Isoglutamine