Anti-Cancer and Stress Response Pathway Effects of Nanosilver and Sodium Ascorbate

Nanosilver (nAg) has superb antimicrobial, antiviral, antifungal, antiparasitic, and anticancer properties; and plays an important role in nanoscience, nanotechnology, and nanomedicine. Smaller nAg particles can enter cells and interact with the cellular components. The exposure dose, particle size, coating, and aggregation state, as well as the cell type or organism, are all large determining factors on the beneficial or toxic effects of nAg. Sodium ascorbate is a vital water-soluble antioxidant that can neutralize free radicals produced during illness. It has pro-oxidant effects in its oxidized form, and in this form is able to destroy cancer cells through the production of hydrogen peroxide. With the growing prevalence of cancer, there is an increasing need to find both new treatments and combinations of treatments to provide greater effectiveness. Nanosilver was found to be more toxic to HCT116 human colon cancer cells (24-hour EC50 of 78.43 ± 0.70 µg/mL) than to HIEC-6 human intestinal epithelial cells (no toxicity was observed for the treatment concentrations tested). Combined treatments of high dose sodium ascorbate with nAg demonstrated significantly increased toxicity to HCT116 cells as opposed to HIEC-6 cells, and increased the cell death from that observed with either of the treatments alone. The novel result was found that it is more toxic to cancer cells to use a combined treatment of high dose sodium ascorbate with low dose of nAg; as opposed to low dose sodium ascorbate with high dose nAg, where a protective effect is seen. Nanosilver induced cell cycle arrest in the G2/M phase in HCT116 cells, and combined treatment with sodium ascorbate further increased this effect. This was found to be a nAg specific effect and did not occur with silver nitrate. Cellular oxidative stress was not induced by nAg, however, mitochondrial oxidative stress was induced in HCT116 cells after 24 hours of treatment. Additionally, no significant effect on mitochondrial oxidative phosphorylation or the cellular ER stress response was found. Combined treatment of nAg with sodium ascorbate may be beneficial in decreasing WNT pathway signalling in cancer cells through the non-canonical pathway involving WNT5A.