title: The p53 inhibitor, pifithrin-α, suppresses self-renewal of embryonic stem cells.
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)-α, an inhibitor of p53-dependent transcriptional activation, on self-renewal of ES cells. Our results revealed that treatment of ES cells with PFT-α 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-α 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.affiliation: Molecular Neuroscience Research Center, Shiga University of Medical Science, Setatsukinowa-cho, Otsu, Shiga 520-2192, Japan. essam_abdelalim@yahoo.com
authors.forename: Essam Mohamed
authors.initials: EM
authors.lastname: Abdelalim
authors.forename: Ikuo
authors.initials: I
authors.lastname: Tooyama
mesh_terms: D000818:Animals; D052160:Benzothiazoles / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival; D019938:Cyclin D1 / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics; D051379:Mice; D000071317:Nanog Homeobox Protein; D014050:Toluene / Q000031:analogs & derivatives* / Q000494:pharmacology; D015533:Transcriptional Activation / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors*
chemical_list: D052160:Benzothiazoles; D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; D014050:Toluene; C121565:pifithrin