β-Catenin Knockdown in Liver Tumor Cells by a Cell Permeable Gamma Guanidine-based Peptide Nucleic Acid.

β-Catenin Knockdown in Liver Tumor Cells by a Cell Permeable Gamma Guanidine-based Peptide Nucleic Acid. Curr Cancer Drug Targets. 2013 Jul 1; Authors: Delgado E, Bahal R, Yang J, Lee JM, Ly DH, Monga SP Abstract Hepatocellular cancer (HCC) is the third cause of death by cancer worldwide. In the current study we target β-catenin, an oncogene mutated and constitutively active in 20-30% of HCCs, via a novel, cell permeable gamma guanidine-based peptide nucleic acid (γGPNA) antisense oligonucleotide designed against either the transcription or the translation start site of the human β-catenin gene. Using TOPflash, a luciferase reporter assay, we show that γGPNA targeting the transcription start site showed more robust activity against β-catenin activity in liver tumor cells that harbor β-catenin gene mutations (HepG2 & Snu-449). We identified concomitant suppression of β-catenin expression and of various Wnt targets including glutamine synthetase (GS) and cyclin-D1. Concurrently, γGPNA treatment reduced proliferation, survival and viability of HCC cells. Intriguingly, an angiogenesis quantitative Real-Time-PCR array identified decreased expression of several pro-angiogenic secreted factors such as EphrinA1, FGF-2, and VEGF-A upon β-catenin inhibition in liver tumor cells. Conversely, transfection of stabilized-β-catenin mutants enhanced the expression of angiogenic factors like VEGF-A. Conditioned media from HepG2 cells treated wit...
Source: Current Cancer Drug Targets - Category: Cancer & Oncology Authors: Tags: Curr Cancer Drug Targets Source Type: research