Author/Authors :
Nagaraju، نويسنده , , Ganji Purnachandra and Zhu، نويسنده , , Shijun and Wen، نويسنده , , Jing and Farris، نويسنده , , Alton B. and Adsay، نويسنده , , Volkan N. and Diaz، نويسنده , , Roberto and Snyder، نويسنده , , James P. and Mamoru، نويسنده , , Shoji and El-Rayes، نويسنده , , Bassel F. Shneker، نويسنده ,
Abstract :
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.
Keywords :
EF31 , Curcumin , pancreatic cancer , UBS109 , DNA methylation
