Fenbendazole induces apoptosis of porcine uterine luminal epithelial and trophoblast cells during early pregnancy

초록

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 antiproliferative molecule that induces critical apoptosis in the porcine trophectoderm and uterine luminal epithelial cells by disrupting the mitochondria membrane potential during early pregnancy. (C) 2019 Published by Elsevier B.V.

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