TY - JOUR
T1 - Ivermectin-induced programmed cell death and disruption of mitochondrial membrane potential in bovine mammary gland epithelial cells
AU - Park, Hahyun
AU - Song, Gwonhwa
AU - Lim, Whasun
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 & Welfare (grant number: HI17C0929 ) and the National Research Foundation of Korea(NRF) grant funded by the Ministry of Science and ICT(MSIT) (No. 2018R1C1B6009048 ).
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 & Welfare (grant number: HI17C0929) and the National Research Foundation of Korea(NRF) grant funded by the Ministry of Science and ICT(MSIT) (No. 2018R1C1B6009048).
PY - 2020/2
Y1 - 2020/2
N2 - 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.
AB - 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.
KW - Ca chelation
KW - Cell signaling pathway
KW - Ivermectin
KW - MMP
KW - Programmed cell death
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U2 - 10.1016/j.pestbp.2019.10.011
DO - 10.1016/j.pestbp.2019.10.011
M3 - Article
C2 - 31973874
AN - SCOPUS:85075346225
SN - 0048-3575
VL - 163
SP - 84
EP - 93
JO - Pesticide Biochemistry and Physiology
JF - Pesticide Biochemistry and Physiology
ER -