Propyl gallate induces cell death and inhibits invasion of human trophoblasts by blocking the AKT and mitogen-activated protein kinase pathways

Propyl gallate (PG) is an antioxidant widely used in food additives, cosmetics, adhesives, and lubricants. PG protects the oils in food products from reacting with hydrogen peroxide and oxygen free radicals, thus preventing spoilage. It is known to have both protective and cytotoxic effects on various cells, but its effects on human trophoblasts remain unclear. Therefore, we investigated the effects of PG on proliferation, apoptosis, and invasiveness of human trophoblasts using an immortalized HTR8/SVneo cell line. We found that PG significantly reduced proliferation of and induced apoptosis in HTR8/SVneo cells. In addition, the invasiveness of HTR8/SVneo cells was attenuated in response to PG. Signaling pathways including the PI3K/AKT and MAPK pathways involved in the proliferation and invasiveness of human trophoblasts were regulated by PG treatment in HTR8/ SVneo cells. We confirmed that mitochondrial membrane disruption and Ca2+ overload were markedly elevated in response to PG treatment, suggesting that PG-induced apoptosis is closely related to mitochondrial dysfunction and further PG-induced apoptosis in HTR8/SVneo cells is related to endoplasmic reticulum (ER) stress. Collectively, these results indicate that PG exerts harmful effects on human trophoblasts; therefore, exposure to PG in early pregnancy is predicted to cause abnormal implantation and placental development.