新型合成姜黄素类似物 EF31 和 UBS109 是胰腺癌中有效的 DNA 低甲基化剂。
Novel synthetic curcumin analogues EF31 and UBS109 are potent DNA hypomethylating agents in pancreatic cancer.
机构信息
Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, United States.
出版信息
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。
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