Flavone acetic acid antitumour activity against a mouse pancreatic adenocarcinoma is mediated by natural killer cells.
Flavone acetic acid (FAA) is one of the most active antitumour agents against mouse solid tumours. A number of reports favour the hypothesis that FAA could behave as a biological response modifier; in fact FAA stimulates natural killer (NK) cells, induces secretion of type I interferon and synergizes with interleukin-2 to increase NK/lymphokine-activated killer (LAK) activity in vivo. However, there is no conclusive evidence that the antitumour activity of FAA is mediated via the modulation of NK/LAK cells. The present study was designed to evaluate whether the reported activation of NK cells is instrumental in FAA antitumour activity. FAA (180 mg/kg, i.v. on days 3, 7 and 11 after tumour implant) was significantly effective in inhibiting the subcutaneous growth of the pancreatic adenocarcinoma PAN/03 in C57/Bl mice. After 132 days the number of tumour-free survivors was 36%, whereas in the control group receiving no treatment, or in the group of mice treated with 10 micrograms/mouse of alpha-asialo-GM1 the value was only 0 or 6.7%, respectively. The combination of FAA and alpha-asialo-GM1 resulted in only 6% tumour-free mice. In parallel experiments, splenocytes and peritoneal cells from C57/B1 mice were tested in a standard cytotoxicity NK assay. While animals treated with FAA showed a significant increase in NK activity, those injected with alpha-asialo-GM1 had very low levels, and the combined treatment of FAA and alpha-asialo-GM1 resulted in a lower or similar NK activity compared to that in untreated mice. The fact that the abrogation of the NK-stimulating effect of FAA is accompanied by a lack of anti-tumour activity indicates that, at least in this experimental model, FAA is likely to act via an immunomodulatory mechanism.
Damia
G
G
Laboratory of Cancer Chemotherapy, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
Tagliabue
G
G
Allavena
P
P
D'Incalci
M
M
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000276:immunology; D000818:Animals; D005419:Flavonoids / Q000494:pharmacology*; D005677:G(M1) Ganglioside; D006028:Glycosphingolipids / Q000494:pharmacology; D007111:Immunity, Cellular / Q000187:drug effects; D007113:Immunity, Innate / Q000187:drug effects; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000276:immunology
D005419:Flavonoids; D006028:Glycosphingolipids; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside; C049328:flavone acetic acid