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

Hye Jin Min, Il Rae Cho, Ratakorn Srisuttee, Eun Hee Park, Dae Ho Cho, Jin Hyun Ahn, Im Soon Lee, Randal N. Johnston, Sangtaek Oh, Young Hwa Chung

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)136-142
Number of pages7
JournalCancer letters
Volume276
Issue number2
DOIs
Publication statusPublished - 2009 Apr 18

Keywords

  • Epstein-Barr virus
  • Hexachlorophene
  • Latent membrane protein (LMP)-1
  • Siah-1
  • β-Catenin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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