Selenite induced breast cancer MCF7 cells apoptosis through endoplasmic reticulum stress and oxidative stress pathway.

Selenium is an essential trace element for human, and has anti-tumor effects. In this study, we investigated the anti-tumor activity of sodium selenite (NaSeO) and explored its possible mechanisms involved in a breast cancer cell line. We found that NaSeO could inhibit the cell viability of MCF7 cells, yet with minimal damage to human umbilical vein endothelial cells (HUVECs). The results of Hoechst staining and Western Blot showed that NaSeO induced apoptosis of MCF7 cells. NaSeO activated endoplasmic reticulum stress (ERS), as evidenced by the up-regulation of ERS-related proteins, including ATF6, p-eIF2α, ATF4, and CHOP, and the down-regulation of PERK. ATF6, p-eIF2α and apoptosis were decreased by pre-treatment with an ERS inhibitor (4-PBA). NaSeO activated oxidative stress (OS) through increasing ROS generation and decreasing mitochondrial membrane potential (MMP) which induced apoptosis. Pre-treatment with an antioxidant (NAC) attenuated NaSeO-induced OS and cell apoptosis. Furthermore, ERS and OS had mutual effects. Pre-treatment with 4-PBA could act against the up-regulation of ROS and the down-regulation of MMP. Pre-treatment with NAC attenuated the expression of ATF6. At the same time, we found that treatment with NaSeO promoted the phosphorylation of p38 and JNK, while inhibiting the phosphorylation of ERK. However, the up-regulation was inhibited after pre-treatment of NAC, and pre-treatment with 4-PBA inhibited the increase only of p38. Based on these results, our study provides a mechanistic understanding of how NaSeO has antitumor effects against MCF7 cells through the OS and ERS pathway. OS and ERS interact with each other, and p38 is regulated by them.