Brouet I, Ohshima H
Unit of Endogenous Cancer Risk Factors, International Agency for Research on Cancer, Lyon, France.
Biochem Biophys Res Commun. 1995 Jan 17;206(2):533-40. doi: 10.1006/bbrc.1995.1076.
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 microM). NOS activity in soluble extracts of macrophages activated for 6-24 h in the presence of curcumin (10 microM) 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.
L-精氨酸衍生的一氧化氮（NO）及其衍生物，如过氧亚硝酸盐和二氧化氮，在炎症中发挥作用，也可能在癌症发生的多阶段过程中起作用。我们研究了各种非甾体抗炎药及相关化合物对脂多糖（LPS）和干扰素-γ（IFN-γ）激活的RAW 264.7巨噬细胞中一氧化氮合酶（NOS）诱导的影响。姜黄素是一种具有抗炎和抗氧化特性的强效抗肿瘤剂，低浓度时可抑制NO生成，以24小时释放到培养基中的亚硝酸盐量衡量（IC50 = 6 microM）。在姜黄素（10 microM）存在下激活6 - 24小时的巨噬细胞可溶性提取物中的NOS活性显著低于未用姜黄素激活的巨噬细胞。Northern印迹和免疫印迹分析表明，与未用姜黄素激活的巨噬细胞相比，用姜黄素激活的巨噬细胞中诱导型NOS的mRNA和130 kDa蛋白水平显著降低。当姜黄素与LPS和IFN-γ一起添加时，对NOS诱导的抑制作用最大，随着姜黄素与LPS/IFN-γ之间的间隔增加到18小时，抑制作用逐渐减弱。
