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 peroxynitrite and nitrogen dioxide, play a role in inflammation and also possibly in the multistage process of carcinogenesis. We investigated the effect of various non-steroidal anti-inflammatory agents and related compounds on the induction of NO synthase (NOS) in RAW 264.7 macrophages activated with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). Low concentrations of curcumin, a potent anti-tumour agent having anti-inflammatory and anti-oxidant properties, inhibited NO production, 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 macrophages activated for 6 - 24 h in the presence of curcumin (10 mu M) was significantly lower than that of macrophages activated without curcumin. Northern-blot and immunoblotting analyses demonstrated that significantly reduced levels of the mRNA and 130-kDa protein of inducible NOS were expressed in macrophages activated with curcumin, compared to those without curcumin. Inhibition of NOS induction was maximal when curcumin was added together with LPS and IFN-gamma, and decreased progressively as the interval between curcumin and LPS/IFN-gamma was increased to 18 h. (C) 1995 Academic Press, Inc.