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

被引:14
作者
Afroze, Syeda H. [1 ]
Sloan, Jenna [2 ]
Osuji, Grace-Ann C. [3 ]
Drever, Nathan [2 ]
Pilkinton, Kimberly [2 ]
Zawieja, David C. [1 ]
Kuehl, Thomas J. [2 ,4 ]
Uddin, M. Nasir [2 ,4 ,5 ]
机构
[1] Texas A&M Hlth Sci Ctr, Dept Med Physiol, Coll Med, Temple, TX USA
[2] Scott & White Hosp, Dept Obstet & Gynecol, Baylor Scott & White Hlth, Texas A&M Hlth Sci Ctr,Coll Med, Bldg 1,Room 352,2401 South 31st St, Temple, TX 76508 USA
[3] Baylor Scott & White Hlth, Dept Clin Pathol, Temple, TX USA
[4] Texas A&M Hlth Sci Ctr, Coll Med, Dept Pediat, Baylor Scott & White Hlth, Temple, TX 76504 USA
[5] Texas A&M Hlth Sci Ctr, Coll Med, Dept Internal Med, Baylor Scott & White Hlth, Temple, TX 76504 USA
关键词
Apoptosis; Cell signaling; Cinobufotalin; Cytotrophoblast; Preeclampsia; RAT MODEL; TROPHOBLAST DIFFERENTIATION; NORMAL-PREGNANCY; SPIRAL ARTERIES; PREECLAMPSIA; MARINOBUFAGENIN; BUFADIENOLIDES; IMPLANTATION; MECHANISMS; BUFALIN;
D O I
10.1007/s11010-016-2820-0
中图分类号
Q2 [细胞生物学];
学科分类号
071013 [干细胞生物学];
摘要
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 aeyen1 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 aeyen1 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.
引用
收藏
页码:189 / 196
页数:8
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