title: Cinobufotalin impedes Sw.71 cytotrophoblast cell line function via cell cycle arrest and apoptotic signaling.
abstract: Preeclampsia (preE) is a hypertensive disorder of pregnancy. Cardiotonic steroids (CTS) are endogenous inhibitors of Na+/K+ATPase, and at least one CTS, marinobufagenin (MBG), is elevated in a rat model of preE prior to the development of the syndrome. MBG and ouabain impair cytotrophoblast (CTB) cell function, which is critical for placental development. We evaluated the effect of a CTS, cinobufotalin (CINO), on CTB cell function in vitro. CINO at ≥1 nM inhibited CTB cell proliferation, migration, and invasion (p < 0.05), but had no effect on cell viability. There was a higher (p < 0.05) percentage of G0/G1 phase cells in groups treated with CINO at ≥1 nM. CINO caused an increase in stress signaling p38 MAPK and a positive annexin-V staining in CTB cells, indicating the activation of apoptotic signaling. However, the CINO-induced apoptotic signaling was prevented by p38 inhibition. These data demonstrate that CINO impairs CTB cell function via cell cycle arrest and apoptotic signaling.
authors.affiliation: Department of Medical Physiology, Texas A&M Health Science Center College of Medicine, Temple, TX, USA.
authors.forename: Syeda H
authors.initials: SH
authors.lastname: Afroze
authors.affiliation: Department of Obstetrics and Gynecology, Baylor Scott & White Health/Texas A&M Health Science Center College of Medicine, Scott & White Hospital (Building 1), Room #352, 2401 South 31st Street, Temple, TX, 76508, USA.
authors.forename: Jenna
authors.initials: J
authors.lastname: Sloan
authors.affiliation: Department of Clinical Pathology, Baylor Scott & White Health, Temple, TX, USA.
authors.forename: Grace-Ann C
authors.initials: GC
authors.lastname: Osuji
authors.affiliation: Department of Obstetrics and Gynecology, Baylor Scott & White Health/Texas A&M Health Science Center College of Medicine, Scott & White Hospital (Building 1), Room #352, 2401 South 31st Street, Temple, TX, 76508, USA.
authors.forename: Nathan
authors.initials: N
authors.lastname: Drever
authors.affiliation: Department of Obstetrics and Gynecology, Baylor Scott & White Health/Texas A&M Health Science Center College of Medicine, Scott & White Hospital (Building 1), Room #352, 2401 South 31st Street, Temple, TX, 76508, USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Pilkinton
authors.affiliation: Department of Medical Physiology, Texas A&M Health Science Center College of Medicine, Temple, TX, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Zawieja
authors.affiliation: Department of Obstetrics and Gynecology, Baylor Scott & White Health/Texas A&M Health Science Center College of Medicine, Scott & White Hospital (Building 1), Room #352, 2401 South 31st Street, Temple, TX, 76508, USA.|Department of Pediatrics, Baylor Scott & White Health/Texas A&M Health Science Center College of Medicine, Temple, TX, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Kuehl
authors.affiliation: Department of Obstetrics and Gynecology, Baylor Scott & White Health/Texas A&M Health Science Center College of Medicine, Scott & White Hospital (Building 1), Room #352, 2401 South 31st Street, Temple, TX, 76508, USA. Mohammad.uddin1@BSWHealth.org.|Department of Pediatrics, Baylor Scott & White Health/Texas A&M Health Science Center College of Medicine, Temple, TX, USA. Mohammad.uddin1@BSWHealth.org.|Department of Internal Medicine, Baylor Scott & White Health/Texas A&M Health Science Center College of Medicine, Temple, TX, USA. Mohammad.uddin1@BSWHealth.org.
authors.forename: M
authors.initials: M
authors.lastname: Nasir Uddin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002018:Bufanolides / Q000494:pharmacology*; D002460:Cell Line; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D011225:Pre-Eclampsia / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D051381:Rats; D014327:Trophoblasts / Q000378:metabolism* / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D002018:Bufanolides; D048051:p38 Mitogen-Activated Protein Kinases; C063451:cinobufotalin
keywords: Apoptosis; Cell signaling; Cinobufotalin; Cytotrophoblast; Preeclampsia