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

Cancer Lett 2009 Apr 16;276(2):136-42. Epub 2008 Dec 16.

Department of Nanomedical Engineering, BK21 Nanofusion Technology Team, Pusan National University, Miryang, Gyeongnam, Republic of Korea.

Many studies have shown that the activation of beta-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 beta-catenin and cellular transformation. Conversely, results from cell-based small molecule screening studies have shown that the antibiotic hexachlorophene can down-regulate beta-catenin in colon cancer cells. Here we report that hexachlorophene also counteracts the elevated beta-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 beta-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 beta-catenin is independent of p53 and results in reduced expression of cyclin-D1 and c-Myc (target genes of beta-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 beta-catenin levels via the restoration of Siah-1.

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Source
https://linkinghub.elsevier.com/retrieve/pii/S03043835080087
Publisher Site
http://dx.doi.org/10.1016/j.canlet.2008.10.041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116996PMC
April 2009

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