Novel synthetic curcumin analogues EF31 and UBS109 are potent DNA hypomethylating agents in pancreatic cancer
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- 作者：Ganji Purnach ; ra Nagaraju ; Shijun Zhu ; Jing Wen ; Alton B. Farris ; Volkan N. Adsay ; Roberto Diaz ; James P. Snyder ; Shoji Mamoru ; Bassel F. El-Rayes
- 关键词：DNMT-1 ; DNA methyltransferase-1 ; HSP90 ; heat shock protein 90 ; SPARC ; secreted protein acidic and rich in cysteine ; DAPI ; 4&prime ; -6-diamidino-2-phenylindole
- 刊名：Cancer Letters
- 出版年：1 December, 2013
- 年：2013
- 卷：341
- 期：2
- 页码：195-203
- 全文大小：2402 K
文摘
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-魏B 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.