Induction of S-phase arrest and p21 overexpression by a small molecule 2[[3-(2,3-dichlorophenoxy)propyl] amino]ethanol in correlation with activation of ERK

Hongbo Zhu, Lidong Zhang, Shuhong Wu, Fuminori Teraishi, John J. Davis, Dietmar Jacob, Bingliang Fang

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

We recently found that a small molecule 2[[3-(2,3-dichlorophenoxy)propyl] amino]ethanol (2,3-DCPE) could induce apoptosis and downregulate Bel-XL expression in various cancer cells. Here, we found that 2,3-DCPE suppressed the proliferation of Bcl-XL-overexpressing cancer cells without inducing apoptosis. Subsequently, we found that 2,3-DCPE could induce S-phase arrest and upregulate p21 but not p27 at a time- and dose-dependent but p53-dispensable manner in DLD-1 human colon cancer cells. Activation of ERK was also detected after treatment with 2,3-DCPE. Moreover, p21 induction was dramatically attenuated by ERK inhibitors PD98059 and U0126. Induction of p21 and S-phase arrest and corresponding activation of ERK were also observed in ATM-defective cells, suggesting that 2,3-DCPE-induced these events were ATM-dispensable. Furthermore, ERK inhibitors dramatically attenuated 2,3-DCPE-induced S-phase arrest. Together, our data indicate that ERK activation correlated with the 2,3-DCPE-mediated induction of p21 expression and S-phase arrest. This finding may have implication for cancer therapy.

Original languageEnglish
Pages (from-to)4984-4992
Number of pages9
JournalOncogene
Volume23
Issue number29
DOIs
Publication statusPublished - Jun 24 2004
Externally publishedYes

Keywords

  • ATM
  • ERK
  • S-phase arrest
  • Small molecule
  • p21
  • p53

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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