Study of Cytotoxic and Therapeutic Effects of Silver Nanoparticles against Colon Tumor Cells
Silver nanoparticles (Ag NPs) have antimicrobial activity and therapeutic effects that have led to their wide range of applications in the medical field. With a drastic increase in the advancement and utilization of AgNP based therapeutic agents there is a dire need for rational design of AgNPs and study of their cytotoxic effects in order to develop safer and more effective therapies. We synthesized and characterized 43.2 ± 12.1 nm Ag NPs that are stable (non-aggregating) in cell culture medium up to 120 h, and investigated the time and dose dependent uptake and cytotoxicity of Ag NPs on human colon tumor cells. A dose and time dependence were shown in the growth of tumor cells treated with 2.5, 5, and 20 pM Ag NPs with significant decrease in cell population in Ag NP treated cells compared to control after 120 h (p<0.05). No growth inhibition was seen in the blank control experiments for the tumor cells treated with the supernatant (absence of Ag NPs). We also studied the underlying molecular mechanisms of the inhibitory effects of Ag NPs upon the growth of the tumor cells. We found that the Ag NPs induced cell cycle arrest and/or inhibition, genotoxicity, and apoptosis. The number of individual Ag NPs taken up by metabolically active cells over time were quantitatively analyzed and showed fewer Ag NPs in the nucleus than the cytoplasm. The number of accumulated NPs in the nucleus remained constant while the total number of cytoplasm NPs increased over 72 h after which, they began to decline suggesting efflux of Ag NPs from the cells might have occurred. This study offers new insight into the underlying cytotoxic mechanism of Ag NPs against colon tumor cells and demonstrates the potential therapeutic effects of stable and purified Ag NPs against tumors.