Pharmacological inhibition of polycomb repressive complex-2 activity induces apoptosis in human colon cancer stem cells. Academic Article uri icon

Overview

MeSH

  • Animals
  • Cell Survival
  • Enzyme Activation
  • Epigenesis, Genetic
  • Fluorescent Antibody Technique, Indirect
  • HT29 Cells
  • Histones
  • Humans
  • In Situ Nick-End Labeling
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Phosphorylation
  • Promoter Regions, Genetic
  • SOXB1 Transcription Factors
  • Treatment Outcome
  • Xenograft Model Antitumor Assays

MeSH Major

  • Apoptosis
  • PTEN Phosphohydrolase
  • Polycomb Repressive Complex 2

abstract

  • Colorectal cancer is among the leading causes of cancer death in the USA. The polycomb repressive complex 2 (PRC2), including core components SUZ12 and EZH2, represents a key epigenetic regulator of digestive epithelial cell physiology and was previously shown to promote deleterious effects in a number of human cancers, including colon. Using colon cancer stem cells (CCSC) isolated from human primary colorectal tumors, we demonstrate that SUZ12 knockdown and treatment with DZNep, one of the most potent EZH2 inhibitors, increase apoptosis levels, marked by decreased Akt phosphorylation, in CCSCs, while embryonic stem (ES) cell survival is not affected. Moreover, DZNep treatments lead to increased PTEN expression in these highly tumorigenic cells. Taken together, our findings suggest that pharmacological inhibition of PRC2 histone methyltransferase activity may constitute a new, epigenetic therapeutic strategy to target highly tumorigenic and metastatic colon cancer stem cells. Copyright © 2013 Elsevier Inc. All rights reserved.

publication date

  • June 10, 2013

has subject area

  • Animals
  • Apoptosis
  • Cell Survival
  • Enzyme Activation
  • Epigenesis, Genetic
  • Fluorescent Antibody Technique, Indirect
  • HT29 Cells
  • Histones
  • Humans
  • In Situ Nick-End Labeling
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • PTEN Phosphohydrolase
  • Phosphorylation
  • Polycomb Repressive Complex 2
  • Promoter Regions, Genetic
  • SOXB1 Transcription Factors
  • Treatment Outcome
  • Xenograft Model Antitumor Assays

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3880229

Digital Object Identifier (DOI)

  • 10.1016/j.yexcr.2013.04.006

PubMed ID

  • 23588203

Additional Document Info

start page

  • 1463

end page

  • 1470

volume

  • 319

number

  • 10