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Title: The p53 inhibitor, pifithrin-{alpha}, suppresses self-renewal of embryonic stem cells

Abstract

Highlights: Black-Right-Pointing-Pointer We determine the role of p53 in ES cells under unstressful conditions. Black-Right-Pointing-Pointer PFT-{alpha} suppresses ES cell proliferation. Black-Right-Pointing-Pointer PFT-{alpha} induces ES cell cycle arrest. Black-Right-Pointing-Pointer PFT-{alpha} downregulates Nanog and cyclin D1. -- Abstract: Recent studies have reported the role of p53 in suppressing the pluripotency of embryonic stem (ES) cells after DNA damage and blocking the reprogramming of somatic cells into induced pluripotent stem (iPS) cells. However, to date no evidence has been presented to support the function of p53 in unstressed ES cells. In this study, we investigated the effect of pifithrin (PFT)-{alpha}, an inhibitor of p53-dependent transcriptional activation, on self-renewal of ES cells. Our results revealed that treatment of ES cells with PFT-{alpha} resulted in the inhibition of ES cell propagation in a dose-dependent manner, as indicated by a marked reduction in the cell number and colony size. Also, PFT-{alpha} caused a cell cycle arrest and significant reduction in DNA synthesis. In addition, inhibition of p53 activity reduced the expression levels of cyclin D1 and Nanog. These findings indicate that p53 pathway in ES cells rather than acting as an inactive gene, is required for ES cell proliferation and self-renewal under unstressful conditions.

Authors:
 [1]
  1. Molecular Neuroscience Research Center, Shiga University of Medical Science, Setatsukinowa-cho, Otsu, Shiga 520-2192 (Japan)
Publication Date:
OSTI Identifier:
22207804
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 420; Journal Issue: 3; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CELL CYCLE; CELL PROLIFERATION; DNA; DNA DAMAGES; GENES; INHIBITION; NEOPLASMS; STEM CELLS

Citation Formats

Abdelalim, Essam Mohamed, E-mail: essam_abdelalim@yahoo.com, Department of Cytology and Histology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522, and Tooyama, Ikuo. The p53 inhibitor, pifithrin-{alpha}, suppresses self-renewal of embryonic stem cells. United States: N. p., 2012. Web. doi:10.1016/J.BBRC.2012.03.041.
Abdelalim, Essam Mohamed, E-mail: essam_abdelalim@yahoo.com, Department of Cytology and Histology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522, & Tooyama, Ikuo. The p53 inhibitor, pifithrin-{alpha}, suppresses self-renewal of embryonic stem cells. United States. https://doi.org/10.1016/J.BBRC.2012.03.041
Abdelalim, Essam Mohamed, E-mail: essam_abdelalim@yahoo.com, Department of Cytology and Histology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522, and Tooyama, Ikuo. 2012. "The p53 inhibitor, pifithrin-{alpha}, suppresses self-renewal of embryonic stem cells". United States. https://doi.org/10.1016/J.BBRC.2012.03.041.
@article{osti_22207804,
title = {The p53 inhibitor, pifithrin-{alpha}, suppresses self-renewal of embryonic stem cells},
author = {Abdelalim, Essam Mohamed, E-mail: essam_abdelalim@yahoo.com and Department of Cytology and Histology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522 and Tooyama, Ikuo},
abstractNote = {Highlights: Black-Right-Pointing-Pointer We determine the role of p53 in ES cells under unstressful conditions. Black-Right-Pointing-Pointer PFT-{alpha} suppresses ES cell proliferation. Black-Right-Pointing-Pointer PFT-{alpha} induces ES cell cycle arrest. Black-Right-Pointing-Pointer PFT-{alpha} downregulates Nanog and cyclin D1. -- Abstract: Recent studies have reported the role of p53 in suppressing the pluripotency of embryonic stem (ES) cells after DNA damage and blocking the reprogramming of somatic cells into induced pluripotent stem (iPS) cells. However, to date no evidence has been presented to support the function of p53 in unstressed ES cells. In this study, we investigated the effect of pifithrin (PFT)-{alpha}, an inhibitor of p53-dependent transcriptional activation, on self-renewal of ES cells. Our results revealed that treatment of ES cells with PFT-{alpha} resulted in the inhibition of ES cell propagation in a dose-dependent manner, as indicated by a marked reduction in the cell number and colony size. Also, PFT-{alpha} caused a cell cycle arrest and significant reduction in DNA synthesis. In addition, inhibition of p53 activity reduced the expression levels of cyclin D1 and Nanog. These findings indicate that p53 pathway in ES cells rather than acting as an inactive gene, is required for ES cell proliferation and self-renewal under unstressful conditions.},
doi = {10.1016/J.BBRC.2012.03.041},
url = {https://www.osti.gov/biblio/22207804}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 3,
volume = 420,
place = {United States},
year = {Fri Apr 13 00:00:00 EDT 2012},
month = {Fri Apr 13 00:00:00 EDT 2012}
}