Synthesis of Silver Nanoparticles from the Polysaccharide of Farfarae Flos and Uncovering Its Anticancer Mechanism Based on the Cell Metabolomic Approach.

ABSTRACT

In this study, the polysaccharide of Farfarae Flos (FFP) was utilized as a reducing agent to the green synthesis of FFP@AgNPs, and the anticancer activity was evaluated using the HT29 cells. The results showed that the FFP@AgNPs could significantly decrease proliferation ability, inhibit migration, and promote cell apoptosis of HT29 cells, which suggested that the FFP@AgNPs showed significant, strong cytotoxicity against HT29 cells. The cell metabolomic analysis coupled with the heatmap showed an obvious metabolome difference for the cells with and without FFP@AgNPs treatment, which was related to 51 differential metabolites. Four metabolic pathways were determined as the key pathways, and the representative functional metabolites and metabolic pathways were validated in vitro. Nicotinic acid (NA) was revealed as the key metabolite relating with the effect of FFP@AgNPs, and it was interesting that NA supplementation could inhibit the proliferation ability of HT29 cells in vitro, lead to mitochondrial dysfunction, reduce intracellular ATP, and damage the integrity of the cell membrane, which exhibited a similar effect as FFP@AgNPs. In conclusion, this study not only revealed the anticancer mechanism of FFP@AgNPs against the HT29 cells but also provided the important reference that NA shows a potential role in the development of a therapy for colorectal cancer.