Anticancer Potential of Doxorubicin in Combination with Green-Synthesized Silver Nanoparticle and its Cytotoxicity Effects on Cardio-Myoblast Normal Cells.

Abstract

The use of DOX as an anticancer agent is associated with serious side effects on normal cells especially in cardiovascular tissue. Here, it is proposed that the combination of a low dose of DOX with AgNPs provides ideal cytotoxicity against cancer cells and decreases side effects on normal human cells. This study evaluates the cytotoxic effects of green-synthetized AgNPs (GS-AgNPs) in combination with DOX in cancerous cells (MCF7) and investigates its influences on cell growth and apoptosis in a normal cell line of the heart (H9c2). We used coffee extracts, as a reducing and stabilizing agent for the green-synthesis of AgNPs. GSAgNPs were characterized by using various analytical methods. MTT assay was used for cell toxicity analysis in cancerous and normal cells. Moreover, Annexin-V /PI staining and mRNA expression of Bax, Bcl2 and p53 were performed for apoptosis measurement in heart normal cell line. GS-AgNPs showed more biocompatibility for normal cells and higher cytotoxicity for cancerous cells compared to that reported for chemically synthesized nanoparticles. Our results also demonstrated that a selected combination of DOX and AgNPs, 20 μM AgNPs / 0.3 μM DOX, had a suitable cytotoxic effect against cancerous cells with a minimum toxic effect on normal cells. So, no significant alteration was observed in cell migration capacity, apoptosis and gene expression of BAX, Bcl-2 and P53 when H9c2 cells were treated with 20 μM AgNPs / 0.3 μM DOX relative to the non-treated control. Finally, it seems that the combination of GS-AgNPs and DOX could be a potent strategy to combat cancer.