Muramyl peptides augment cytotoxic effect of tumor necrosis factor-alpha in combination with cytotoxic drugs on tumor cells.
We have demonstrated that biologically active muramyl peptides, in particular, glucosaminylmuramyl dipeptide (GMDP), augmented in vitro cytotoxic activity of tumor necrosis factor-alpha (TNF-alpha) against murine fibrosarcoma L929 cells. The introduction of GMDP resulted in cytotoxic effect characteristic for substantially higher dose of cytokine. Even more potent was the combination of GMDP, TNF-alpha and Actinomycin D (ActD). According to clonogenic and MTT assays 100% L929 cells could be killed in culture with low doses of TNF-alpha and ActD if GMDP was present. When cisplatin was substituted for ActD similar results were obtained. GMDP also enhanced cytotoxicity of TNF-alpha and cisplatin against human breast carcinoma MCF7 and histiocytic lymphoma U937 cells. Normal cells, namely human peripheral blood leucocytes and murine peritoneal macrophages, were resistant to selected doses of TNF-alpha/cisplatin/GMDP.
Petrova
Elena E
EE
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Sciences, Moscow, Russia.
Valyakina
Tatiana I
TI
Simonova
Maria A
MA
Komaleva
Ravilya L
RL
Khaidukov
Sergey V
SV
Makarov
Eugene A
EA
Blokhin
Dmitry Yu
DY
Ivanov
Pavel K
PK
Andronova
Tatiana M
TM
Nesmeyanov
Vladimir A
VA
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000633:toxicity; D000276:Adjuvants, Immunologic / Q000633:toxicity*; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002945:Cisplatin / Q000633:toxicity; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D003609:Dactinomycin / Q000633:toxicity; D004359:Drug Therapy, Combination; D006801:Humans; D007739:L Cells; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity*; D020298:U937 Cells
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C063429:glucosaminylmuramyl-2-alanine-D-isoglutamine; D002945:Cisplatin