Cinobufotalin impedes Sw.71 cytotrophoblast cell line function via cell cycle arrest and apoptotic signaling

• Published in: Molecular and cellular biochemistry Vol. 422; no. 1-2; pp. 189 - 196
• Main Authors: Afroze, Syeda H., Sloan, Jenna, Osuji, Grace-Ann C., Drever, Nathan, Pilkinton, Kimberly, Zawieja, David C., Kuehl, Thomas J., Nasir Uddin, M.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.11.2016; Springer; Springer Nature B.V
• Subjects: Analysis; Animals; Apoptosis; Apoptosis - drug effects; Biochemistry; Biomedical and Life Sciences; Bufanolides - pharmacology; Cardiology; Cell cycle; Cell Line; Cells; Female; G1 Phase Cell Cycle Checkpoints - drug effects; Humans; Hypertension; Life Sciences; MAP Kinase Signaling System - drug effects; Medical Biochemistry; Oncology; Ouabain; p38 Mitogen-Activated Protein Kinases - metabolism; Pre-Eclampsia - metabolism; Pre-Eclampsia - pathology; Pregnancy; Rats; Signal transduction; Trophoblasts - metabolism; Trophoblasts - pathology; Cytotrophoblast; Preeclampsia; Cell signaling; Cinobufotalin; Apoptosis
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-016-2820-0

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.