TY - JOUR
T1 - Homosalate aggravates the invasion of human trophoblast cells as well as regulates intracellular signaling pathways including PI3K/AKT and MAPK pathways
AU - Yang, Changwon
AU - Lim, Whasun
AU - Bazer, Fuller W.
AU - Song, Gwonhwa
N1 - Funding Information:
This work was supported by grants from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (No. HI15C0810 awarded to G.S. and HI17C0929 awarded to W.L.).
Publisher Copyright:
© 2018 Elsevier Ltd
PY - 2018/12
Y1 - 2018/12
N2 - Homosalate is an organic ultraviolet filter used in most sunscreens but has been reported to be toxic to marine organisms. The estrogenic activity of homosalate has also been reported, but its endocrine-disrupting effect remains unclear. Although homosalate has been detected in human placental tissues, its effect on the survival of human trophoblast cells needs to be investigated. Therefore, in this study, we evaluated if HTR8/SVneo, a human trophoblast cell line, treated with homosalate showed decreasing proliferative activity in a dose-dependent manner. Homosalate promoted the death of HTR8/SVneo cells with elevated lipid peroxidation and intracellular Ca2+ concentration. It also induced endoplasmic reticulum stress and mitochondrial morphological disturbances associated with the differentiation of human trophoblast cells. However, when the intracellular Ca2+ or reactive oxygen species were removed using BAPTA-AM or N-acetyl-L-cysteine (NAC), the cell proliferation suppressed by homosalate was restored. Homosalate also significantly inhibited the invasion of HTR8/SVneo cells. Furthermore, it modulated phosphoinositide 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK) signaling pathways, which were involved in the cross-talk between both signaling pathways in HTR8/SVneo cells. Thus, homosalate adversely affects the survival, proliferation, and invasiveness of human trophoblast cells and therefore pregnant women should practice caution while using personal care products containing homosalate.
AB - Homosalate is an organic ultraviolet filter used in most sunscreens but has been reported to be toxic to marine organisms. The estrogenic activity of homosalate has also been reported, but its endocrine-disrupting effect remains unclear. Although homosalate has been detected in human placental tissues, its effect on the survival of human trophoblast cells needs to be investigated. Therefore, in this study, we evaluated if HTR8/SVneo, a human trophoblast cell line, treated with homosalate showed decreasing proliferative activity in a dose-dependent manner. Homosalate promoted the death of HTR8/SVneo cells with elevated lipid peroxidation and intracellular Ca2+ concentration. It also induced endoplasmic reticulum stress and mitochondrial morphological disturbances associated with the differentiation of human trophoblast cells. However, when the intracellular Ca2+ or reactive oxygen species were removed using BAPTA-AM or N-acetyl-L-cysteine (NAC), the cell proliferation suppressed by homosalate was restored. Homosalate also significantly inhibited the invasion of HTR8/SVneo cells. Furthermore, it modulated phosphoinositide 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK) signaling pathways, which were involved in the cross-talk between both signaling pathways in HTR8/SVneo cells. Thus, homosalate adversely affects the survival, proliferation, and invasiveness of human trophoblast cells and therefore pregnant women should practice caution while using personal care products containing homosalate.
KW - Apoptosis
KW - Homosalate
KW - Invasion
KW - Proliferation
KW - Trophoblasts
UR - http://www.scopus.com/inward/record.url?scp=85056207345&partnerID=8YFLogxK
U2 - 10.1016/j.envpol.2018.09.092
DO - 10.1016/j.envpol.2018.09.092
M3 - Article
C2 - 30267922
AN - SCOPUS:85056207345
SN - 0269-7491
VL - 243
SP - 1263
EP - 1273
JO - Environmental Pollution
JF - Environmental Pollution
ER -