Role of T cells and tumour necrosis factor in antitumour activity and toxicity of flavone acetic acid.
To investigate the importance of natural killer (NK) and T cells in the inhibition of tumour growth by flavone acetic acid (FAA), colon 26 murine carcinoma was grafted subcutaneously in euthymic and athymic mice. FAA was active in euthymic but not in athymic mice (ratio between tumour weight in treated vs. control animals [T/C %], 27% and 92%, respectively). NK cell activity was increased in both mouse strains, indicating a lack of major involvement of this lymphocyte population in FAA efficacy. In euthymic mice tumour-specific T cells were activated, and after in vivo depletion of lymphocyte subpopulations (L3T4 and Lyt2), tumour inhibition by FAA was abrogated (T/C %, 88%). Antitumour efficacy of FAA was also reduced when the treatment was followed by injection of antitumour necrosis factor alpha (TNF alpha) antibodies. FAA toxicity depended on tumour weight at the time of treatment: 200 mg/kg caused 0 and 100% mortality in mice bearing tumour nodules under 50 and over 300 mg, respectively. When anti-TNF alpha antibodies were given after FAA treatment, the toxicity was greatly reduced (3/14 mice died compared with 10/15).
Pratesi
G
G
Istituto Nazionale per lo Studio de la Cura dei Tumori, Milan, Italy.
Rodolfo
M
M
Rovetta
G
G
Parmiani
G
G
D000230:Adenocarcinoma / Q000097:blood / Q000473:pathology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000920:Antibody-Dependent Cell Cytotoxicity; D000970:Antineoplastic Agents / Q000633:toxicity*; D005419:Flavonoids / Q000633:toxicity*; D007694:Killer Cells, Natural / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000097:blood / Q000473:pathology; D013601:T-Lymphocytes / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D005419:Flavonoids; D014409:Tumor Necrosis Factor-alpha; C049328:flavone acetic acid