Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, United States.
Cancer Lett. 2013 Dec 1;341(2):195-203. doi: 10.1016/j.canlet.2013.08.002. Epub 2013 Aug 7.
DNA methylation is a rational therapeutic target in pancreatic cancer. The activity of novel curcumin analogues EF31 and UBS109 as demethylating agents were investigated. MiaPaCa-2 and PANC-1 cells were treated with vehicle, curcumin, EF31 or UBS109. EF31 and UBS109 resulted in significantly higher inhibition of proliferation and cytosine methylation than curcumin. Demethylation was associated with re-expression of silenced p16, SPARC, and E-cadherin. EF31 and UBS109 inhibited HSP-90 and NF-κB leading to downregulation of DNA methyltransferase-1 (DNMT-1) expression. Transfection experiments confirmed this mechanism of action. Similar results were observed in vitro when subcutaneous tumors (MiaPaCa-2) were treated with EF31 and UBS109.
DNA 甲基化是胰腺癌的一个合理的治疗靶点。本研究考察了新型姜黄素类似物 EF31 和 UBS109 的去甲基化活性。用溶剂、姜黄素、EF31 或 UBS109 处理 MiaPaCa-2 和 PANC-1 细胞。EF31 和 UBS109 导致增殖和胞嘧啶甲基化的抑制明显高于姜黄素。去甲基化与沉默的 p16、SPARC 和 E-钙黏蛋白的重新表达相关。EF31 和 UBS109 抑制 HSP-90 和 NF-κB，导致 DNA 甲基转移酶-1(DNMT-1)表达下调。转染实验证实了这种作用机制。当用 EF31 和 UBS109 处理皮下肿瘤（MiaPaCa-2）时，在体外也观察到了类似的结果。
