Staphylococcal entorotoxin B anchored exosome induces apoptosis in negative esterogen receptor breast cancer cells

Abstract

Exosomes (EXO) are acellular vehicles used for cancer immunotherapy due to their immune inducing properties. To identify whether designed structure based on tumoral EXO have a cytotoxic effect together with a potent immunological property, we synthesized a novel structure based on EXO and staphylococcal entrotoxin B (SEB), two immune inducer substances, and surveyed its cytostatic effect on the breast cancer cell line. EXO were purified from tumor cells and SEB was anchored on it by protein transfer method. To determine the cytotoxic and apoptosis inducing effect of this structure, treated cells with different concentrations of EXO/SEB were examined by MTT assay and Hoechst staining method. In addition, the expression rate of bcl-2, bax, bak, fas, bcl-xl and the activity of caspase-3 and caspase-9 were assessed. We observed that EXO/SEB significantly decreased the cell proliferation and stimulated apoptosis (P < 0.001) at all concentration after 24 h (P < 0.001). Furthermore, EXO/SEB raised the expression rate of bax and bak (P < 0.001) but no impact on fas and bcl-xl after 48 h. We observed reducing effect of EXO/SEB on the mRNA expression of bcl-2. After 24 h of exposing the cell with the EXO/SEB, a significant increase was found in the activity of caspase at the concentration of 2.5, 5 and 10 μg/100 μl for caspase-9 and at all concentrations for caspase-3 (P < 0.001). Our designed structure, the EXO/SEB, is a novel model for apopto-immunotherapy being able to induce apoptosis in ER(-) breast cancer cells.

Texosome-anchored superantigen triggers apoptosis in original ovarian cancer cells

“…Moreover, findings from Hoechst staining showed that the apoptotic effects upon exposure to TEX-SEB are dose dependent. This finding corresponds with the results of our previous works showing the apoptotic activity of SEB-anchored exosome derived from breast cancer [12] and pancreatic cancer cell lines [11]. In those studies, we observed the activation of mitochondrial-dependent apoptosis pathway owing to increasing expression of pro-apoptotic genes involved in bcl2 family and caspase-3 activity.…”

“…Ristrocelli et al [10] suggested exosome-enriched cholesterol, ceramide and sphingomyelin cause caspase-3 and caspase-9 activation. In addition, our previous work indicated the increased activity of described caspases after exposure to exosomel/staphylococcal enterotoxin B [12]. But here we showed no changes in the expression level of pro-apoptotic and anti-apoptotic genes tested here.…”

“…But here we showed no changes in the expression level of pro-apoptotic and anti-apoptotic genes tested here. Previous report intimated that texosome and its derivatives could induce the mitochondrial-dependent apoptotic pathway [10,12]. High level of bax leads to inactivation of the protective function of bcl-2.…”

“…However, it was reported that texosomes from MIA Paca-2 cells, poorly differentiated pancreatic cancer cell line, had no effect on cell proliferation and cell death [9,10]. Additionally, our recent works revealed that SEB-anchored texosome was cytotoxic for pancreatic [11] and breast cancer cell lines [12].…”

Overexpression of Metastatic Related MicroRNAs, Mir-335 and Mir-10b, by Staphylococcal Enterotoxin B in the Metastatic Breast Cancer Cell Line

“…10 Recently, Hosseini et al reported that SEB anchored on Exosomes was able to augment apoptotic genes in the MDA-MB231and Miapaca-2 and induce apoptosis. 11,12 Although the antitumor properties of this superantigen were reported in previous studies, but its effect on the regulation of genes which involved in the cancer progression and metastasis has not been completely revealed. In the following study, we aimed to investigate the effect of SEB on the expression of two microRNAs, mir-335 and mir-10b, which regulate metastasis pathway in breast cancer.…”