4-Methylbenzylidene-camphor inhibits proliferation and induces reactive oxygen species-mediated apoptosis of human trophoblast cells

Reprod Toxicol. 2019 Mar:84:49-58. doi: 10.1016/j.reprotox.2018.12.011. Epub 2018 Dec 28.

Abstract

4-Methylbenzylidene-camphor (4-MBC) is an estrogenic compound used in a variety of personal care products and is associated with water pollution. In this study, we verified that exposure to 4-MBC suppresses the proliferation and invasiveness of the HTR8/SVneo human trophoblast cell line. Moreover, HTR8/SVneo cells treated with 4-MBC underwent apoptosis with increased DNA fragmentation. 4-MBC also activated the PI3K/AKT and ERK1/2 signaling pathways in HTR8/SVneo cells. Furthermore, 4-MBC induced oxidative stress mediated by reactive oxygen species production, which was associated with HTR8/SVneo cell death. 4-MBC promoted lipid peroxidation and loss of mitochondrial membrane potential in HTR8/SVneo cells and activated the expression of genes encoding a protein expressed on the surface of human trophoblast cells, including the EPH receptor B4 and G protein-coupled receptor 56 genes. Therefore, 4-MBC may retard the normal growth and survival of human trophoblast cells and may hamper normal placental formation during early pregnancy.

Keywords: 4-MBC; Apoptosis; Proliferation; ROS; Trophoblast.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Camphor / analogs & derivatives*
  • Camphor / toxicity
  • Cell Line
  • Cell Proliferation / drug effects
  • Estrogens / toxicity*
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Reactive Oxygen Species / metabolism
  • Receptor, EphB4 / genetics
  • Receptors, G-Protein-Coupled / genetics
  • Trophoblasts / drug effects*
  • Trophoblasts / physiology

Substances

  • ADGRG1 protein, human
  • Estrogens
  • Reactive Oxygen Species
  • Receptors, G-Protein-Coupled
  • Camphor
  • enzacamene
  • Receptor, EphB4