TY - JOUR
T1 - Fenbendazole induces apoptosis of porcine uterine luminal epithelial and trophoblast cells during early pregnancy
AU - Park, Hahyun
AU - Lim, Whasun
AU - You, Seungkwon
AU - Song, Gwonhwa
N1 - Funding Information:
This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute funded by the Ministry of Health and Welfare (grant number: HI17C0929 ) and the National Research Foundation of Korea (NRF) grant funded by the Ministry of Science and ICT (MSIT) (No. 2018R1C1B6009048 ).
Publisher Copyright:
© 2019
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2019/9/1
Y1 - 2019/9/1
N2 - Fenbendazole, is an effective benzimidazole anthelmintic that prevents parasite infection in both human and veterinary health care. Although the well-known and effect of benzimidazole was recently shown to have a broad spectrum of biological abilities, such as anticancer and anti-inflammation activities, the mechanism of benzimidazole's antiproliferative effect via cell signaling pathways and its role in preimplantation has not been studied. Therefore, the purpose of this study was to determine the effects of fenbendazole on porcine trophectoderm and luminal epithelial cells. First, we investigated cell viability in response to a low dose of fenbendazole, which highly inhibited cell proliferation. In addition, we investigated apoptotic molecules in the mitochondria, imbalanced intracellular calcium homeostasis, and the expression of some genes involved in apoptosis to explain the decrease in proliferation. Finally, we examined the intracellular mechanisms of fenbendazole by measuring the extracellular signal-regulated kinase, PI3K/AKT, and c-Jun N-terminal kinase signaling proteins by western blot analysis. Our findings suggest that fenbendazole functions as an effective anti-proliferative molecule that induces critical apoptosis in the porcine trophectoderm and uterine luminal epithelial cells by disrupting the mitochondria membrane potential during early pregnancy.
AB - Fenbendazole, is an effective benzimidazole anthelmintic that prevents parasite infection in both human and veterinary health care. Although the well-known and effect of benzimidazole was recently shown to have a broad spectrum of biological abilities, such as anticancer and anti-inflammation activities, the mechanism of benzimidazole's antiproliferative effect via cell signaling pathways and its role in preimplantation has not been studied. Therefore, the purpose of this study was to determine the effects of fenbendazole on porcine trophectoderm and luminal epithelial cells. First, we investigated cell viability in response to a low dose of fenbendazole, which highly inhibited cell proliferation. In addition, we investigated apoptotic molecules in the mitochondria, imbalanced intracellular calcium homeostasis, and the expression of some genes involved in apoptosis to explain the decrease in proliferation. Finally, we examined the intracellular mechanisms of fenbendazole by measuring the extracellular signal-regulated kinase, PI3K/AKT, and c-Jun N-terminal kinase signaling proteins by western blot analysis. Our findings suggest that fenbendazole functions as an effective anti-proliferative molecule that induces critical apoptosis in the porcine trophectoderm and uterine luminal epithelial cells by disrupting the mitochondria membrane potential during early pregnancy.
KW - Apoptosis
KW - Apoptotic factors
KW - Fenbendazole
KW - Inflammation
KW - Porcine cells
KW - Proliferation
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U2 - 10.1016/j.scitotenv.2019.05.116
DO - 10.1016/j.scitotenv.2019.05.116
M3 - Article
C2 - 31102815
AN - SCOPUS:85065581608
SN - 0048-9697
VL - 681
SP - 28
EP - 38
JO - Science of the Total Environment
JF - Science of the Total Environment
ER -