FH535 Potentiation of Cigarette Smoke Condensate Cytotoxicity is Associated With Changes in β-Catenin and EGR-1 Signaling

Abstract

Cigarette smoke condensate (CSC) has been reported to elicit morphological and transcriptional changes that suggest epithelial-to-mesenchymal transition (EMT) in cultured bronchial epithelial cells. The transdifferentiation potential of acute and prolonged CSC exposure alone or in combination with the β-catenin inhibitor, FH535, was investigated in the bronchial epithelial cell line, BEAS-2B, through assessment of cell morphology, transcript expression, protein expression, and protein localization. Changes in morphology, β-catenin translocation, E-cadherin expression, metalloproteinase expression, and fibronectin could be demonstrated independent of molecular or physiological evidence of EMT. FH535 was shown to increase CSC-induced cytotoxicity and depress β-catenin expression. However, FH535 effects were not limited to the β-catenin pathway as it also blocked the expression of early growth responsive protein 1 (EGR-1) target genes, fibronectin and phosphatase and tensin homologue, without affecting EGR-1 nuclear accumulation.

Effect of FH535 on in vitro maturation of porcine oocytes by inhibiting WNT signaling pathway

“…Supplemented with FH535, the protein abundance of β‐catenin was suppressed, which was in accordance with Polk (), Iida et al . () and Liu et al .…”

Effects of cigarette smoke condensate on the production and characterization of exopolysaccharides by Bifidobacterium

“…Cigarette smoke is a complex mixture of over 4700 identified constituents that include numerous reactive substances such as a large quantity of reactive aldehydes, free radical species and diverse metals (Hecht 2006). Cigarette smoke condensate (CSC) has been reported to elicit morphological and transcriptional changes that suggest epithelialto-mesenchymal transition (EMT) in cultured bronchial epithelial cells (Polk 2012). Zonuz et al (2008) reported that the growth of Streptococcus mutans and Streptococcus sanguis is accelerated in the vicinity of CSC.…”