TY - JOUR
T1 - Decanoic acid suppresses proliferation and invasiveness of human trophoblast cells by disrupting mitochondrial function
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 and Welfare , Republic of Korea (No. HI15C0810 awarded to G.S. and HI17C0929 awarded to W.L.).
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 and Welfare, Republic of Korea (No. HI15C0810 awarded to G.S. and HI17C0929 awarded to W.L.).
Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2018/1/15
Y1 - 2018/1/15
N2 - Decanoic acid (DA) is a medium-chain fatty acid used in the manufacture of various products including plastics, cosmetics, and lubricants. In addition to antiviral and antibacterial effects, DA's, reported biological activities include regulation of signaling pathways and redox homeostasis in various human cell types. The influence of DA on functional properties of human trophoblasts, including proliferation, invasion and apoptosis is currently unknown. In the present study, we evaluated the anti-proliferative and anti-invasive effects of DA on the human trophoblast cell line HTR8/SVneo. In addition, DA induced oxidative stress, as evidenced by generation of reactive oxygen species (ROS) and induction of lipid peroxidation (LPO). This oxidative stress was accompanied by activation of the mitochondria-dependent apoptotic pathway in HTR8/SVneo cells. We also observed elevated mitochondrial Ca2 +, and loss of mitochondrial membrane potential in response to DA treatment. Chelation of mitochondrial Ca2 + using BAPTA-AM rescued cellular proliferation suppressed by DA. We also verified that signaling proteins including AKT, P70S6K, S6, and ERK1/2 and their targets were significantly reduced in HTR8/SVneo cells by DA treatment. Pre-treatment of cells with selective inhibitors of AKT (LY294002) and ERK1/2 (U0126) revealed that the AKT and ERK1/2 signaling pathways regulated by DA displayed cross-talk in HTR8/SVneo cells. Collectively, these results suggest that personal products containing DA will have harmful effects on human trophoblasts, and could cause implantation and placentation failure during early pregnancy.
AB - Decanoic acid (DA) is a medium-chain fatty acid used in the manufacture of various products including plastics, cosmetics, and lubricants. In addition to antiviral and antibacterial effects, DA's, reported biological activities include regulation of signaling pathways and redox homeostasis in various human cell types. The influence of DA on functional properties of human trophoblasts, including proliferation, invasion and apoptosis is currently unknown. In the present study, we evaluated the anti-proliferative and anti-invasive effects of DA on the human trophoblast cell line HTR8/SVneo. In addition, DA induced oxidative stress, as evidenced by generation of reactive oxygen species (ROS) and induction of lipid peroxidation (LPO). This oxidative stress was accompanied by activation of the mitochondria-dependent apoptotic pathway in HTR8/SVneo cells. We also observed elevated mitochondrial Ca2 +, and loss of mitochondrial membrane potential in response to DA treatment. Chelation of mitochondrial Ca2 + using BAPTA-AM rescued cellular proliferation suppressed by DA. We also verified that signaling proteins including AKT, P70S6K, S6, and ERK1/2 and their targets were significantly reduced in HTR8/SVneo cells by DA treatment. Pre-treatment of cells with selective inhibitors of AKT (LY294002) and ERK1/2 (U0126) revealed that the AKT and ERK1/2 signaling pathways regulated by DA displayed cross-talk in HTR8/SVneo cells. Collectively, these results suggest that personal products containing DA will have harmful effects on human trophoblasts, and could cause implantation and placentation failure during early pregnancy.
KW - Decanoic acid
KW - Invasion
KW - Mitochondria
KW - Proliferation
KW - Trophoblast
UR - http://www.scopus.com/inward/record.url?scp=85038219974&partnerID=8YFLogxK
U2 - 10.1016/j.taap.2017.12.009
DO - 10.1016/j.taap.2017.12.009
M3 - Article
C2 - 29248464
AN - SCOPUS:85038219974
SN - 0041-008X
VL - 339
SP - 121
EP - 132
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
ER -