Effect of flavone acetic acid (NSC 347,512) on splenic cytotoxic effector cells and their role in tumour necrosis

Abstract

Flavone acetic acid (FAA), an antitumour agent currently undergoing clinical trial, has immune-modulatory effects on various cytotoxic cells in mice. Natural killer (NK) cell activity in the spleen was augmented 4 h after FAA treatment, and when spleen cells were cultured with interleukin-2 to induce the production of lymphokine-activated-killer (LAK) cells, higher levels of LAK cell activity were generated by spleen cells from FAA-treated animals than by spleen cells from untreated, control mice. The response to FAA by spleen cells from mice bearing the Colon 38 tumour was compared to that of non-tumour bearers. Activity against NK-sensitive YAC-1 tumour targets was augmented to a similar degree, and no activity against NK-resistant P815 targets was detected. FAA was shown to induce haemorrhagic necrosis in the P815 tumour grown as a subcutaneous solid tumour. Furthermore, haemorrhagic necrosis was induced by FAA on Colon 38 tumours growing in mice which had been depleted of NK activity by treatment with anti-asialo GM-1 antibody. Thus, although NK activity could be involved in the long-term host response to the tumour, it does not appear to be a major determinant of FAA-induced haemorrhagic tumour necrosis.