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Hexachlorophene suppresses β-catenin expression by up-regulation of Siah-1 in EBV-infected B lymphoma cells

Many studies have shown that the activation of β-catenin signaling can promote oncogenesis, and it is therefore of interest to find agents that modulate this pathway. Recent work has shown using B lymphoma cells that infection by Epstein–Barr virus (EBV) and expression of its latent membrane protein...

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Detalles Bibliográficos
Autores principales: Min, Hye-Jin, Cho, Il-Rae, Srisuttee, Ratakorn, Park, Eun-Hee, Cho, Dae Ho, Ahn, Jin-Hyun, Lee, Im-Soon, Johnston, Randal N., Oh, Sangtaek, Chung, Young-Hwa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Ireland Ltd. 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116996/
https://www.ncbi.nlm.nih.gov/pubmed/19091460
http://dx.doi.org/10.1016/j.canlet.2008.10.041
Descripción
Sumario:Many studies have shown that the activation of β-catenin signaling can promote oncogenesis, and it is therefore of interest to find agents that modulate this pathway. Recent work has shown using B lymphoma cells that infection by Epstein–Barr virus (EBV) and expression of its latent membrane protein (LMP)-1, cause increases in the expression of β-catenin and cellular transformation. Conversely, results from cell-based small molecule screening studies have shown that the antibiotic hexachlorophene can down-regulate β-catenin in colon cancer cells. Here we report that hexachlorophene also counteracts the elevated β-catenin levels in EBV-infected B lymphomas. This is associated with restoration in levels of Siah-1 (an E3 ubiquitin ligase that is active in β-catenin regulation) which had been diminished by LMP-1. Our results suggest that Siah-1 is targeted by both LMP-1 and hexachlorophene with opposite effects. The hexachlorophene modulation of Siah-1 and β-catenin is independent of p53 and results in reduced expression of cyclin-D1 and c-Myc (target genes of β-catenin), leading to the growth arrest of B lymphoma cells. From these results we propose that hexachlorophene may provide a novel therapeutic strategy for EBV-infected B lymphoma cells by reducing β-catenin levels via the restoration of Siah-1.