Synergistic effect of Ebselen and gamma radiation on breast cancer cells

Purpose: To explore the synergistic effect of a seleno-organic compound Ebselen (Ebs) and/or -radiation to exert antitumor effects on human breast cancer (MCF-7) cell line in vitro. Materials and methods: Ebs cytotoxicity at various concentrations (10, 25, 50 and 75 mu g), cell proliferation and clonogenic assay of Ebs and/or gamma-radiation (at 1, 3 and 6Gy), expression of p-I kappa B alpha and NF-kappa B, inflammatory cytokines levels (TNF-alpha, IL-2, INF-gamma, IL-10 and TGF-beta), apoptotic factors (Caspase-3, Granzyme-B and TRAIL) and angiogenic factor (VEGF) were investigated. Results: The results showed that the effective dosage of this combination was observed at 25 mu g/ml of Ebs with gamma-radiation at 6Gy. Data displayed a significant reduction in NF-kappa B mRNA along with an elevation in granzyme-B mRNA and TRAIL mRNA expression. Furthermore, protein expression of caspase-3 was elevated, whereas p-I kappa B alpha and p-NF-kappa B(p65) protein expression was reduced significantly. Also, a significant decline in TNF-alpha, IL-2, INF-gamma, TGF-beta with a significant increase in IL-10 levels were revealed. Meanwhile, a significant decrease in VEGF level and proliferation capacity were observed. Conclusions: We conclude that a combination of Ebs with radiotherapy has a major antitumor efficiency in inducing apoptosis and inhibiting cancer cell progression, due to the synergistic effect in regulating gene and protein expression, and in a modulating response of pro-and anti-inflammatory cytokines.