CURCUMIN, AN ANTITUMOR PROMOTER AND ANTIINFLAMMATORY AGENT, INHIBITS INDUCTION OF NITRIC-OXIDE SYNTHASE IN ACTIVATED MACROPHAGES

L-Arginine-derived nitric oxide (NO) and its derivatives, such as pero xynitrite and nitrogen dioxide, play a role in inflammation and also p ossibly in the multistage process of carcinogenesis. We investigated t he effect of various non-steroidal anti-inflammatory agents and relate d compounds on the induction of NO synthase (NOS) in RAW 264.7 macroph ages activated with lipopolysaccharide (LPS) and interferon-gamma (IFN -gamma). Low concentrations of curcumin, a potent anti-tumour agent ha ving anti-inflammatory and anti-oxidant properties, inhibited NO produ ction, as measured by the amount of nitrite released into the culture medium in 24 h (IC50 = 6 mu M). NOS activity in soluble extracts of ma crophages activated for 6 - 24 h in the presence of curcumin (10 mu M) was significantly lower than that of macrophages activated without cu rcumin. Northern-blot and immunoblotting analyses demonstrated that si gnificantly reduced levels of the mRNA and 130-kDa protein of inducibl e NOS were expressed in macrophages activated with curcumin, compared to those without curcumin. Inhibition of NOS induction was maximal whe n curcumin was added together with LPS and IFN-gamma, and decreased pr ogressively as the interval between curcumin and LPS/IFN-gamma was inc reased to 18 h. (C) 1995 Academic Press, Inc.