Abstract

Exosomes (EXOs) are nanovesicles secreted by all cell types, which can be used as an acellular strategy for cancer immunotherapy. Application of superantigens (SAgs) as an adjuvant enhances the immune responses created by EXOs. In addition, it is reported that the combination of SAgs with EXOs derived from cancer cells causes the induction of mitochondrial apoptosis. In the current study, we aimed to analysis the effect of EXOs with or without SAg on the endoplasmic reticulum (ER) mediated apoptosis. We anchored staphylococcal enterotoxin B (SEB) on EXOs isolated from a triple negative breast cancer cell line (EXO/SEB). Then, to identify the impact of EXO/SEB on the induction of ER apoptosis, MDA MB-231 cell line was treated with 25, 50 and 100 mu g/ml EXO/SEB, EXO and SEB for 24 h and the expression ratio of GRP-78, CHOP and IRE-1 was assessed using real-time PCR and the fold change expression was assessed by Rest 2009. Exposing the cells to 100 mu g/ml EXOs and 25 mu g/ml EXO/SEB remarkably increased GRP-78 expression (p < 0.001). Furthermore, the ratio of CHOP expression was considerably raised after treatment with 50 and 100 mu g/ml EXO/SEB (p < 0.001). On the other hand, our observation demonstrated a significant increase in the IRE-1 expression ratio at the concentration of 25, 50 and 100 mu g/ml of EXO/SEB (21.99, 13.1 and 9.82 fold) (p < 0.001). We concluded that EXO/SEB is able to induce ER mediated apoptosis via increased expression of CHOP and IRE-1 genes.