Department of Surgery, Morriston Hospital, ABM University NHS Trust, Morriston, Swansea, UK.
Clin Transl Oncol. 2012 Apr;14(4):302-11. doi: 10.1007/s12094-012-0799-x.
Curcumin has been suggested to possess anti-neoplastic properties. As oesophageal adenocarcinoma (OA) and Barrett's oesophagus (BO) represent a neoplastic series, we postulated that curcumin supplementation may slow neoplastic progression at this site. Our aim was to investigate the effects of curcumin in vitro and in vivo on markers of oesophageal cancer progression.
We investigated the in vitro ability of curcumin to prevent bile acid-induced DNA damage using micronucleus assay and nuclear factor-kappaB (NF-κB) activity in the oesophageal cell lines (OE33) using real-time PCR of the extracted RNA. We also analysed NF-κB p65 activation in curcumin-pre-treated OE33 cells exposed to deoxycholic acid (DCA) using ELISA. In another pilot study, BO patients took a daily 500 mg curcumin tablet for 7 days prior to their endoscopy. In biopsies collected from these patients (n=33, 16 curcumin, 17 control), we examined NF-κB-driven gene expression (interleukin (IL)-8, inhibitor- kappaB (I-κB)) using real-time PCR of the extracted RNA from the biopsy sample. The apoptotic frequency was assessed by counting the number of apoptotic bodies in the epithelial cells from the Barrett's tissue with and without curcumin.
In vitro, curcumin (50 μM) significantly abrogated DNA damage and NF-κB activity induced by bile. Pretreating OE33 cells with curcumin (50 μM) completely abolished the ability of DCA (300 μM) to activate NF-κB. In vivo, IL-8 expression was non-significantly suppressed in the curcumin-supplemented patients compared to the squamous control tissue, whilst also showing a doubling in the apoptotic frequency compared to non-supplemented control patients.
Curcumin abrogated bile-driven effects in vitro. The in vivo data also suggests that curcumin supplementation had beneficial effects (increased apoptosis, potentially reduced NF-κB activity) in the Barrett's tissues themselves, despite poor delivery of the curcumin to the oesophagus.
姜黄素具有抗肿瘤特性。由于食管腺癌（OA）和 Barrett 食管（BO）代表了一种肿瘤系列，我们假设姜黄素补充可能会减缓该部位的肿瘤进展。我们的目的是研究姜黄素在体外和体内对食管癌进展标志物的影响。
我们使用微核试验研究了姜黄素在体外预防胆汁酸诱导的 DNA 损伤的能力，并使用提取 RNA 的实时 PCR 研究了食管细胞系（OE33）中的核因子-κB（NF-κB）活性。我们还使用 ELISA 分析了姜黄素预处理的 OE33 细胞暴露于脱氧胆酸（DCA）时 NF-κB p65 的激活。在另一项试点研究中，BO 患者在接受内镜检查前 7 天每天服用 500mg 姜黄素片。在这些患者（n=33，16 例姜黄素，17 例对照组）的活检中，我们使用提取自活检样本的 RNA 的实时 PCR 研究了 NF-κB 驱动的基因表达（白细胞介素（IL）-8、抑制剂-κB（I-κB））。通过计算有和没有姜黄素的 Barrett 组织上皮细胞中的凋亡小体数量来评估凋亡频率。
在体外，姜黄素（50μM）显著阻断了胆汁诱导的 DNA 损伤和 NF-κB 活性。用姜黄素（50μM）预处理 OE33 细胞完全阻断了 DCA（300μM）激活 NF-κB 的能力。在体内，与鳞状对照组织相比，姜黄素补充组的 IL-8 表达无显著抑制，而与未补充对照组相比，凋亡频率增加了一倍。
姜黄素阻断了体外胆汁驱动的作用。体内数据还表明，尽管姜黄素在食管中的输送较差，但姜黄素补充对 Barrett 组织本身具有有益作用（增加凋亡，潜在降低 NF-κB 活性）。
