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 (Na2SeO3) and explored its possible mechanisms involved in a breast cancer cell line. We found that Na2SeO3 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 Na2SeO3 induced apoptosis of MCF7 cells. Na2SeO3 activated endoplasmic reticulum stress (ERS), as evidenced by the up-regulation of ERS-related proteins, including ATF6, p-eIF2 alpha, ATF4, and CHOP, and the downregulation of PERK. ATF6, p-eIF2 alpha and apoptosis were decreased by pre-treatment with an ERS inhibitor (4PBA). Na2SeO3 activated oxidative stress (OS) through increasing ROS generation and decreasing mitochondrial membrane potential (MMP) which induced apoptosis. Pre-treatment with an antioxidant (NAC) attenuated Na2SeO3-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 Na2SeO3 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 Na2SeO3 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.

Automated summary

Sodium selenite (Na2SeO3) exhibits anti-tumor activity in MCF7 cells by inducing apoptosis and activating the endoplasmic reticulum stress pathway. Oxidative stress and endoplasmic reticulum stress interact to regulate the survival of cancer cells.