Rao C V, Rivenson A, Simi B, Reddy B S
Division of Nutritional Carcinogenesis, American Health Foundation, Valhalla, New York 10595.
Cancer Res. 1995 Jan 15;55(2):259-66.
Human epidemiological and laboratory animal model studies have suggested that nonsteroidal antiinflammatory drugs reduce the risk of development of colon cancer and that the inhibition of colon carcinogenesis is mediated through the alteration in cyclooxygenase metabolism of arachidonic acid. Curcumin, which is a naturally occurring compound, is present in turmeric, possesses both antiinflammatory and antioxidant properties, and has been tested for its chemopreventive properties in skin and forestomach carcinogenesis. The present study was designed to investigate the chemopreventive action of dietary curcumin on azoxymethane-induced colon carcinogenesis and also the modulating effect of this agent on the colonic mucosal and tumor phospholipase A2, phospholipase C gamma 1, lipoxygenase, and cyclooxygenase activities in male F344 rats. At 5 weeks of age, groups of animals were fed the control (modified AIN-76A) diet or a diet containing 2000 ppm of curcumin. At 7 weeks of age, all animals, except those in the vehicle (normal saline)-treated groups, were given two weekly s.c. injections of azoxymethane at a dose rate of 15 mg/kg body weight. All groups were continued on their respective dietary regimen until the termination of the experiment at 52 weeks after the carcinogen treatment. Colonic tumors were evaluated histopathologically. Colonic mucosa and tumors were analyzed for phospholipase A2, phospholipase C gamma 1, ex vivo prostaglandin (PG) E2, cyclooxygenase, and lipoxygenase activities. The results indicate that dietary administration of curcumin significantly inhibited incidence of colon adenocarcinomas (P < 0.004) and the multiplicity of invasive (P < 0.015), noninvasive (P < 0.01), and total (invasive plus noninvasive) adenocarcinomas (P < 0.001). Dietary curcumin also significantly suppressed the colon tumor volume by > 57% compared to the control diet. Animals fed the curcumin diet showed decreased activities of colonic mucosal and tumor phospholipase A2 (50%) and phospholipase C gamma 1 (40%) and levels of PGE2 (> 38%). The formation of prostaglandins such as PGE2, PGF2 alpha, PGD2, 6-keto PGF1 alpha, and thromboxane B2 through the cyclooxygenase system and production of 5(S)-, 8(S)-, 12(S)-, and 15(S)-hydroxyeicosatetraenoic acids via the lipoxygenase pathway from arachidonic acid were reduced in colonic mucosa and tumors of animals fed the curcumin diet as compared to control diet. Although the precise mechanism by which curcumin inhibits colon tumorigenesis remains to be elucidated, it is likely that the chemopreventive action, at least in part, may be related to the modulation of arachidonic acid metabolism.
人类流行病学和实验动物模型研究表明，非甾体抗炎药可降低结肠癌的发病风险，且对结肠癌发生的抑制作用是通过改变花生四烯酸的环氧化酶代谢来介导的。姜黄素是一种天然存在的化合物，存在于姜黄中，具有抗炎和抗氧化特性，并已在皮肤和前胃癌变的化学预防特性方面进行了测试。本研究旨在探讨膳食姜黄素对雄性F344大鼠中由氧化偶氮甲烷诱导的结肠癌发生的化学预防作用，以及该试剂对结肠黏膜和肿瘤中磷脂酶A2、磷脂酶Cγ1、脂氧合酶和环氧化酶活性的调节作用。5周龄时，将动物分组，分别喂食对照（改良AIN - 76A）饮食或含有2000 ppm姜黄素的饮食。7周龄时，除接受赋形剂（生理盐水）处理的组外，所有动物每周皮下注射两次氧化偶氮甲烷，剂量为15 mg/kg体重。所有组均继续其各自的饮食方案，直至致癌物处理后52周实验结束。对结肠肿瘤进行组织病理学评估。分析结肠黏膜和肿瘤中的磷脂酶A2、磷脂酶Cγ1、体外前列腺素（PG）E2、环氧化酶和脂氧合酶活性。结果表明，膳食给予姜黄素可显著抑制结肠腺癌的发生率（P < 0.004）以及侵袭性（P < 0.015）、非侵袭性（P < 0.01）和总（侵袭性加非侵袭性）腺癌的多发性（P < 0.001）。与对照饮食相比，膳食姜黄素还显著抑制结肠肿瘤体积超过57%。喂食姜黄素饮食的动物结肠黏膜和肿瘤中的磷脂酶A2活性（降低50%）、磷脂酶Cγ1活性（降低40%）以及PGE2水平（降低> 38%）均有所下降。与对照饮食相比，喂食姜黄素饮食的动物结肠黏膜和肿瘤中通过环氧化酶系统形成的前列腺素如PGE2、PGF2α、PGD2、6 - 酮PGF1α和血栓素B2以及通过脂氧合酶途径由花生四烯酸产生的5(S)-、8(S)-、12(S)-和15(S)-羟基二十碳四烯酸均减少。尽管姜黄素抑制结肠肿瘤发生的确切机制仍有待阐明，但这种化学预防作用至少部分可能与花生四烯酸代谢的调节有关。
