Journal
CANCER LETTERS
Volume 341, Issue 2, Pages 195-203Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2013.08.002
Keywords
Curcumin; EF31; UBS109; DNA methylation; Pancreatic cancer
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Funding
- Georgia Cancer Coalition [00026700]
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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-kappa 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. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
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