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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

Oncogene volume 23, pages 4984–4992 (2004)Cite this article

Abstract

We recently found that a small molecule 2[[3-(2,3-dichlorophenoxy)propyl]amino]ethanol (2,3-DCPE) could induce apoptosis and downregulate Bcl-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.

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Abbreviations

2,3-DCPE:

2[[3-(2,3-dichlorophenoxy)propyl] amino] ethanol

2,3-DCEE:

2[[3-(2,3-dichlorophenoxy)ethyl]amino] ethanol

DMSO:

dimethyl sulfoxide

p21:

p21WAF1

ERK:

extracellular signal-regulated kinase

ATM:

ataxia telangiectasia-mutated

PBST:

phosphate-buffered saline plus 0.05% Tween-20

PCR:

polymerase chain reaction

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Acknowledgements

We thank David Galloway for editorial review and Jesse C Null for assistance in preparing the manuscript. This article represents partial fulfillment of the requirements for a PhD degree for JJD. This work was supported in part by grants from the National Cancer Institute (RO1 CA 092487-01A1 and RO1 CA 098582-01A1, to BF), a grant from The WM Keck Foundation, and a Core Grant from the National Institutes of Health (CA16672).

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  1. Contributed equally to the paper.

Authors and Affiliations

  1. Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

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

  2. Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, 310016, China

    Hongbo Zhu

  3. Program in Gene Therapy and Virology, The University of Texas Graduate School of Biomedical Sciences, Houston, 77030, TX, USA

    John J Davis & Bingliang Fang

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  1. Hongbo Zhu
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Correspondence to Bingliang Fang.

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Zhu, H., Zhang, L., Wu, S. et al. 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. Oncogene 23, 4984–4992 (2004). https://doi.org/10.1038/sj.onc.1207645

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