Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.
Cancer Prev Res (Phila). 2011 Mar;4(3):354-64. doi: 10.1158/1940-6207.CAPR-10-0098.
Curcumin is derived from the spice tumeric and has antiinflammatory and antineoplastic effects in vitro and in animal models, including preventing aberrant crypt foci (ACF) and adenomas in murine models of colorectal carcinogenesis. Inhibiting the production of the procarcinogenic eicosanoids prostaglandin E₂ (PGE₂) and 5-hydroxyeicosatetraenoic acid (5-HETE) can suppress carcinogenesis in rodents. Curcumin reduces mucosal concentrations of PGE₂ (via inhibition of cyclooxygenases 1 and 2) and 5-HETE (via inhibition of 5-lipoxygenase) in rats. Although preclinical data support curcumin activity in many sites, the poor bioavailability reported for this agent supports its use in the colorectum. We assessed the effects of oral curcumin (2 g or 4 g per day for 30 days) on PGE₂ within ACF (primary endpoint), 5-HETE, ACF number, and proliferation in a nonrandomized, open-label clinical trial in 44 eligible smokers with eight or more ACF on screening colonoscopy. We assessed pre- and posttreatment concentrations of PGE₂ and 5-HETE by liquid chromatography tandem mass spectroscopy in ACF and normal-tissue biopsies; ACF number via rectal endoscopy; proliferation by Ki-67 immunohistochemistry; and curcumin concentrations by high-performance liquid chromatography in serum and rectal mucosal samples. Forty-one subjects completed the study. Neither dose of curcumin reduced PGE₂ or 5-HETE within ACF or normal mucosa or reduced Ki-67 in normal mucosa. A significant 40% reduction in ACF number occurred with the 4-g dose (P < 0.005), whereas ACF were not reduced in the 2-g group. The ACF reduction in the 4-g group was associated with a significant, five-fold increase in posttreatment plasma curcumin/conjugate levels (versus pretreatment; P = 0.009). Curcumin was well tolerated at both 2 g and 4 g. Our data suggest that curcumin can decrease ACF number, and this is potentially mediated by curcumin conjugates delivered systemically.
姜黄素源自香料姜黄，具有抗炎和抗肿瘤作用，在体外和动物模型中均有作用，包括预防结直肠癌变的鼠模型中的异常隐窝病灶（ACF）和腺瘤。抑制前致癌类二十烷酸前列腺素 E₂（PGE₂）和 5-羟二十碳四烯酸（5-HETE）的产生可抑制啮齿动物的癌变。姜黄素可降低大鼠黏膜中 PGE₂（通过抑制环氧化酶 1 和 2）和 5-HETE（通过抑制 5-脂氧合酶）的浓度。尽管临床前数据支持姜黄素在许多部位的活性，但该药物的生物利用度较差，支持其在结直肠中的应用。我们评估了口服姜黄素（每天 2 克或 4 克，持续 30 天）对筛查结肠镜检查中 8 个以上 ACF 的 44 名合格吸烟者的 ACF 内 PGE₂（主要终点）、5-HETE、ACF 数量和增殖的影响。我们通过液相色谱串联质谱法评估了 ACF 和正常组织活检中 PGE₂和 5-HETE 的预处理和治疗后浓度；直肠内镜检查的 ACF 数量；Ki-67 免疫组化的增殖；以及血清和直肠黏膜样本中的高效液相色谱中的姜黄素浓度。41 名受试者完成了研究。两种剂量的姜黄素均未降低 ACF 或正常黏膜中的 PGE₂或 5-HETE，也未降低正常黏膜中的 Ki-67。4 克剂量组的 ACF 数量显著减少 40%（P < 0.005），而 2 克组的 ACF 未减少。4 克组的 ACF 减少与治疗后血浆姜黄素/缀合物水平显著增加五倍相关（与预处理相比；P = 0.009）。2 克和 4 克剂量的姜黄素均耐受良好。我们的数据表明，姜黄素可以减少 ACF 的数量，这可能是通过全身递送至姜黄素缀合物介导的。
