Synergistic effect of Ebselen and gamma radiation on breast cancer cells

Abstract

Purpose: To explore the synergistic effect of a seleno-organic compound Ebselen (Ebs) and/or γ-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 μg), cell proliferation and clonogenic assay of Ebs and/or γ-radiation (at 1, 3 and 6 Gy), expression of p-IκBα and NF-κB, inflammatory cytokines levels (TNF-α, IL-2, INF-γ, IL-10 and TGF-β), 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 μg/ml of Ebs with γ-radiation at 6 Gy. Data displayed a significant reduction in NF-κB mRNA along with an elevation in granzyme-B mRNA and TRAIL mRNA expression. Furthermore, protein expression of caspase-3 was elevated, whereas p-IκBα and p-NF-κB(p65) protein expression was reduced significantly. Also, a significant decline in TNF-α, IL-2, INF-γ, TGF-β 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.

Keywords:

• Ebselen
• γ-radiation
• MCF-7
• NF-κB
• IL-10
• TRAIL

Disclosure statement

No potential conflict of interest was reported by the authors.

Notes on contributors

Noura M. Thabet and Enas M. Moustafa are Lecturers of Radiation Biology Department in National Centre for Radiation Research and Technology at Egyptian Atomic Energy Authority. Their studies focused on the effect of radiation exposure on a biological system through study the physiological and biochemical change accompany after that exposure in case of normal and disease (such as cancer). Their latest publications include: Beta-sitosterol upregulated paraoxonase-1 via peroxisome proliferator-activated receptor-γ in irradiated rats (Can J Physiol Pharmacol, Published on the web 24 January 2017, http://dx.doi.org/10.1139/cjpp-2016-0397); Protective role of Krill oil against estrogen deficiency induced neurodegeneration in ovariectomized rats (IJEB, 2017, 55: 279–285); and Boswellic acid disables signal transduction of IL-6?STAT-3 in Ehrlich ascites tumor bearing irradiated mice (Biochem Cell Biol, 2016, 94: 307?313).