学术报告 9
Molecular mechanisms involved in chemoprevention
of black raspberry extracts: from transcription factors to their target genes.
涉及化学预防黑 覆盆子提取物的分子机制:从转录因子到其靶基因。
原文链接官方网址:https://www.ncbi.nlm.nih.gov/pubmed
Lu H1, Li J, Zhang D, Stoner GD, Huang C.
Nelson Institute of Environmental Medicine, New York University School of
Medicine, Tuxedo, NY 10987, USA.
纳尔逊环境医学研究所,纽约大学医学院,Tuxedo,纽约 10987,美国。
Berries have attracted attention for their chemopreventive activities in last a few years. Dietary freeze-dried blackberries have been shown to reduce esophagus and colon cancer development induced by chemical carcinogen in rodents. To elucidate molecular mechanisms involved in chemoprevention by berry extracts, we employed mouse epidermal Cl 41 cell line, a well-characterized in vitro model in tumor promotion studies. Pretreatment of Cl 41 cells with methanol-extracted blackberry fraction RO-ME resulted in a dramatical inhibition of B(a)PDE-induced activation of AP-1 and NFkB, and expression of VEGF and COX-2. The inhibitory effects of RO-ME on B(a)PDE-induced activation of AP-1 and NFkappaB appear to be mediated via inhibition of MAPKs and IkappaBalpha phosphorylation, respectively. In view of the important roles of AP-1, NFkappaB, VEGF and COX-2 in tumor promotion/progression, and VEGF and COX-2 are target of AP-1 and NFkappaB, we anticipate that the ability of black raspberries to inhibit tumor development may be mediated by impairing signal transduction pathways leading to activation of AP-1 and NFkappaB, subsequently resulting in down-regulation of VEGF and COX-2 expression. The RO-ME fraction appears to be the major fraction responsible for the inhibitory activity of black raspberries.
在过去的几年里,浆果已经引起了他们化学预防活动的关注。已经表明饮食冷冻干燥的黑莓 能够减少啮齿动物中由化学致癌物引起的食管和结肠癌的发展。为了阐明浆果提取物化学预 防涉及的分子机制,我们使用了小鼠表皮细胞株,这是一种在肿瘤促进研究中具有良好特征 的体外模型。用甲醇提取的黑莓级分 RO-ME 预处理 Cl41 细胞导致显着抑制 B(a)PDE 诱导的 AP-1 和 NFkB 活化以及 VEGF 和 COX-2 的表达。RO-ME 对 B(a)PDE 诱导的 AP-1 和 NFκB 活化的抑制作用似乎分别通过 MAPKs 和 IkappaBalpha 磷酸化的抑制来介 导。鉴于 AP-1,NFkappaB 的重要作用,抑制肿瘤发展的黑覆盆子可能通过损伤导致 AP-1 和 NFkappaB 激活的信号转导途径来介导,随后导致 VEGF 和 COX-2 表达的下调。RO-ME 部分似乎是负责黑覆盆子抑制活性的主要部分。
源自:
美国国家医学图书馆
美国国家卫生研究院
US National Library of Medicine/
Us National Institutes of Health/