Singh A K, Sidhu G S, Deepa T, Maheshwari R K
Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Cancer Lett. 1996 Oct 1;107(1):109-15. doi: 10.1016/0304-3835(96)04357-1.
We have studied the effect of curcumin (diferuloylmethane), a major component of the food flavor turmeric, on the proliferation and cell cycle progression of human umbilical vein endothelial cells (HUVEC). Curcumin inhibited the DNA synthesis of HUVEC as revealed by [3H]thymidine incorporation in a dose-dependent manner without significantly affecting the viability of the cells. The growth of HUVEC stimulated with fibroblast growth factor (FGF) and endothelial growth supplement (ECGS) was also inhibited by curcumin. Addition of curcumin to HUVEC resulted in an accumulation of > 46% of the cells in early S-phase, as determined by the FACS analysis. Pulse labeling studies with [3H]thymidine demonstrated that curcumin affected cells that were actively undergoing DNA synthesis. The de-novo synthesis of thymidine depends on thymidine kinase (TK) enzyme. Curcumin caused a significant loss of TK activity, which may be one of the possible mechanism(s) for the inhibition of DNA synthesis activity of HUVEC by curcumin. These studies have revealed a unique mode of action of curcumin whereby it effectively blocked the cell cycle progression during S-phase by inhibiting the activity of TK enzyme. The migration, proliferation and differentiation of HUVEC leads to angiogenesis, which facilitates the tumor initiation and promotion. Since curcumin inhibited the proliferation of HUVEC, it could turn out to be a very useful compound for the development of novel anti-cancer therapy.
我们研究了姜黄素（二阿魏酰甲烷），一种食品香料姜黄的主要成分，对人脐静脉内皮细胞（HUVEC）增殖和细胞周期进程的影响。如通过[3H]胸苷掺入所显示的，姜黄素以剂量依赖的方式抑制HUVEC的DNA合成，而对细胞活力没有显著影响。姜黄素也抑制了用成纤维细胞生长因子（FGF）和内皮生长补充剂（ECGS）刺激的HUVEC的生长。通过流式细胞仪分析确定，向HUVEC中添加姜黄素导致超过46%的细胞在S期早期积累。用[3H]胸苷进行的脉冲标记研究表明，姜黄素影响正在积极进行DNA合成的细胞。胸苷的从头合成依赖于胸苷激酶（TK）酶。姜黄素导致TK活性显著丧失，这可能是姜黄素抑制HUVEC DNA合成活性的可能机制之一。这些研究揭示了姜黄素的一种独特作用方式，即它通过抑制TK酶的活性有效地阻断了S期的细胞周期进程。HUVEC的迁移、增殖和分化导致血管生成，这促进了肿瘤的起始和发展。由于姜黄素抑制了HUVEC的增殖，它可能成为开发新型抗癌疗法的一种非常有用的化合物。
