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

• Published in: Biochemical and biophysical research communications 2012-04, Vol.420 (3)
• Main Authors: Abdelalim, Essam Mohamed, Department of Cytology and Histology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522, Tooyama, Ikuo
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; CELL CYCLE; CELL PROLIFERATION; DNA; DNA DAMAGES; GENES; INHIBITION; NEOPLASMS; STEM CELLS
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/J.BBRC.2012.03.041

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.