Combinatorial drug delivery has shown promising results over single drug for cancer therapy. Here, we aimed to explore combination of proteasome inhibitor; bortezomib (BTZ) with natural antioxidants (AOs); polyphenols like caffeic acid (CFA), resveratrol (RES), fucoidan (FD), and synthetic AO; sodium selenite (NaSeO) for cellular cytotoxicity in breast cancer cell lines; MCF-7 and MDA MB-231. The combination of RES + BTZ, FD + BTZ, and NaSeO + BTZ showed synergism while CFA showed antagonism with BTZ. The EC values of different combinations were found to be significantly less than the individual AOs in ABTS and DPPH assay. Furthermore, the effect of combination of drugs on migratory properties of MCF-7 cells were evaluated by in-vitro wound healing assay, resulting in the reduction of such behavior. In support of this, RT-qPCR was performed to analyze differential gene expressions of apoptotic and Epithelial-Mesenchymal Transition (EMT) markers with and without treatment. In results, the combination of NaSeO + BTZ reduced the expression of Bcl-XL and N-Cad causing cytotoxicity and suggested that the combination of NaSeO + BTZ (IC = 1.40 ± 0.45 μM) could be a better option among other combinations for breast cancer therapy. Overall, the outcome indicates that the combination of BTZ with AOs may yield potential therapeutic benefit.
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