Ivermectin-induced programmed cell death and disruption of mitochondrial membrane potential in bovine mammary gland epithelial cells,Pesticide Biochemistry and Physiology

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Ivermectin-induced programmed cell death and disruption of mitochondrial membrane potential in bovine mammary gland epithelial cells
Pesticide Biochemistry and Physiology ( IF 4.2 ) Pub Date : 2020-02-01 , DOI: 10.1016/j.pestbp.2019.10.011
Hahyun Park ₁ , Gwonhwa Song ₁ , Whasun Lim ₂

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Ivermectin (IVM) is a commercially well-known antiparasitic agent derived from the natural fermentation product avermectin. Originally used as a veterinary drug, IVM has been studied for its pharmacokinetic advantages, such as anticancer, antimigration, and antiproliferative effects, using several cell types. In the present study, we verified that IVM suppressed bovine mammary gland epithelial cell proliferation and induced the arrest of the cell cycle from the sub-G1 to the G2/M phase in these cells. Due to IVM treatment, the homeostasis of calcium ions, which play a crucial role in intracellular metabolism, deteriorated, leading to the loss of the mitochondrial membrane potential (MMP). To underpin these results, further studies using inhibitors of Ca2+ signaling were performed; combination treatment with IVM and these factors, including 2-APB, BAPTA-AM, or ruthenium red, inhibited the IVM-induced MMP disruption. Furthermore, following IVM treatment, the relationships among various cell signaling mediators were altered, and the balance between diverse cellular processes associated with cell survival or death was disturbed. In conclusion, we assessed the anti-survival effects of IVM on mammary gland epithelial cells; IVM may impede normal lactation in dairy cows.

中文翻译：

伊维菌素诱导牛乳腺上皮细胞程序性细胞死亡和线粒体膜电位破坏

伊维菌素 (IVM) 是一种商业上众所周知的抗寄生虫剂，来源于天然发酵产物阿维菌素。IVM 最初用作兽药，已使用多种细胞类型对其药代动力学优势进行了研究，例如抗癌、抗迁移和抗增殖作用。在本研究中，我们证实 IVM 抑制牛乳腺上皮细胞增殖并诱导这些细胞从亚 G1 期到 G2/M 期的细胞周期停滞。由于 IVM 治疗，在细胞内代谢中起关键作用的钙离子的稳态恶化，导致线粒体膜电位 (MMP) 的丧失。为了支持这些结果，使用 Ca2+ 信号传导抑制剂进行了进一步研究；联合 IVM 和这些因素，包括 2-APB，BAPTA-AM 或钌红可抑制 IVM 诱导的 MMP 破坏。此外，在 IVM 治疗后，各种细胞信号传导介质之间的关系发生了改变，与细胞存活或死亡相关的不同细胞过程之间的平衡受到了干扰。总之，我们评估了 IVM 对乳腺上皮细胞的抗存活作用；IVM 可能会阻碍奶牛的正常泌乳。

更新日期：2020-02-01

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