Opposing Effects of Indomethacin and Nordihydroguaiaretic Acid on Macrophage Function and Tumor Growth

The effects of indomethacin (INDO) and nordihydroguaiaretic acid (NDGA) were compared on macrophage function and tumor growth. Intraperitoneal injections (5 mg/kg/day, 6, 8 or 9 days) of INDO in C57BL/6 mice stimulated the cytotoxicity of peritoneal macrophages and inhibited growth of subcutaneous B16 melanoma, whereas NDGA injections suppressed macrophage cytotoxicity, increased macrophage prostaglandin‐E(2) (PGE(2)) release, and enhanced the tumor growth. Further, pretreatment of macrophages in vitro with the INDO group serum increased cytostasis against B16 tumor cells, while the use of NDGA group serum reduced it. Incubation of tumor‐bearer's macrophages in vitro with INDO (10(‐6)M and 10(‐7)M) or 10(‐6)M NDGA for 4 h reduced PGE(2) release, but 10 (‐7)M NDGA markedly enhanced the PGE(2) release. Our data indicate that INDO and NDGA are able to modulate the macrophage function directly, and produce opposing effects on macrophage function and tumor growth. Inhibitory actions of INDO and NDGA on the cyclooxygenase or lipoxygenase pathway of arachidonic acid metabolism appear to contribute to their effects.