Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
Food Chem Toxicol. 2010 Aug-Sep;48(8-9):2265-72. doi: 10.1016/j.fct.2010.05.059. Epub 2010 May 25.
Curcumin, a major component from tumeric and well-known dietary spice, possesses various pharmacological effects. The cancer chemoprevention effect is suggested to act through its pro-oxidant property. The study was to clarify effects of curcumin on cholangiocarcinoma cells, a cancer of the bile duct that refractory to chemotherapeutic drugs. We examined time-course of oxidant formation in relation to antitumor and the adaptive antioxidant response of the cells. Curcumin induced antiproliferation and apoptosis in KKU-M214 CCA cells with concentration- and time- dependent manners. The antiproliferative effect of curcumin was observed at concentrations as low as 3 microM and was not necessarily associated with oxidative stress, while induction of apoptosis required significant production of superoxide anion, suppression of cellular redox and collapse of mitochondrial transmembrane potential. Western blot analysis showed a temporal relationship between the suppression of nuclear NF-kappaB with Bcl-XL protein levels. Up-regulation of p53 and Bax was associated with marked oxidative stress and apoptosis. Curcumin also induced Nrf2 protein expression with up-regulation of gamma-glutamylcysteine ligase mRNA and increased cellular antioxidant, glutathione. The study suggests that curcumin could be developed into an effective chemoprevention against CCA.
姜黄素是姜黄的主要成分，也是一种广为人知的食用香料，具有多种药理作用。其抗癌的化学预防作用被认为是通过其促氧化剂的特性发挥作用的。本研究旨在阐明姜黄素对胆管癌细胞（一种对化疗药物有抗药性的癌症）的影响。我们研究了与抗肿瘤和细胞适应性抗氧化反应相关的氧化剂形成的时程。姜黄素以浓度和时间依赖的方式诱导 KKU-M214 CCA 细胞的增殖抑制和细胞凋亡。姜黄素的增殖抑制作用在低至 3 μM 的浓度下即可观察到，而不一定与氧化应激有关，而细胞凋亡的诱导则需要超氧阴离子的大量产生、细胞内氧化还原的抑制以及线粒体跨膜电位的崩溃。Western blot 分析显示，核 NF-κB 与 Bcl-XL 蛋白水平的抑制之间存在时间关系。p53 和 Bax 的上调与明显的氧化应激和细胞凋亡有关。姜黄素还诱导 Nrf2 蛋白表达，增加 γ-谷氨酰半胱氨酸连接酶 mRNA 和细胞内抗氧化剂谷胱甘肽的水平。该研究表明，姜黄素可能被开发为一种有效的胆管癌化学预防药物。
