Tanshinone IIA induces oxidative stress in trophoblast cells and enhances copper dependent death.

Oxidative stress occurs in trophoblast cells during the development of tubal pregnancy (TP), compared to normal pregnancy. It has been demonstrated that previous studies have shown that Tanshinone IIA (TSA) can increase reactive oxygen species (ROS) levels and exacerbate oxidative stress in tumor cells, while its effects on trophoblast cells or affects cuproptosis pathways remain unclear. We collected chorionic tissue from patients with normal intrauterine pregnancies (NP) or TP to detect the expression of related proteins. HTR-8/SVneo cells were cultured in vitro and treated with Elesclomol, CuCl2 and/or TSA, tetrathiomolybdate (TTM). The expressions of proteins such as DLAT, DLST, FDX1, Lipo-DLAT, Lipo-DLST, Bax, and Bcl-2 were measured. Mitochondrial membrane potential, cell apoptosis, and cell function were also assessed. The concentration of TSA added to HTR8-SVneo cells was 30 µM. The protein expression of DLAT, DLST, Lipo-DLAT, Lipo-DLST monomers, FDX1 and Bcl-2/ Bax was downregulated by the addition of Elesclomol and CuCl(2) intervention in the cells. Meanwhile, the levels of reactive oxygen species (ROS) increased, mitochondrial membrane potential decreased, cell apoptosis increased, and cell invasion and migration were attenuated. The addition of TSA enhanced these effects, while the addition of TTM mitigated them. TSA can promote oxidative stress in HTR-8/SVneo cells, leading to cell apoptosis. This process can be reversed by copper chelator.