An investigation into mechanisms of action of colchicine, zinc acetate and paracetemol - potential candidates for drug repurposing in head and neck cancer therapy

摘要

The incidence of head and neck cancers (HNC) is on the rise. The common therapies used, are associated with long-term toxicities that hamper the quality of life of HNC patients. Novel therapeutic strategies are required to reduce these. As drug discovery is expensive, time consuming and unreliable, in this project we have considered drug repurposing. Paracetemol, zinc acetate and colchicine are used for pain relief, common cold lozenges and gout treatment, respectively. We initially assessed their efficacy on the proliferation of a HNC cell line, SCC040, using an Alamar blue colometric assay. Results indicate zinc acetate significantly inhibited proliferation (62.68 ± 3.75% reduction, p≤0.001) compared to vehicle control. Secondly cell cycle analysis was carried out using propidium iodide staining and flow cytometry analysis. Colchicine was found to be a potent G2/M cell cycle blocker (p≤0.001) compared to its untreated control. Finally the effect of the drugs on the migration of SCC040 cells was assessed using a wound-healing assay. Colchicine was found to significantly inhibit migration compared to its vehicle control (79.55 ± 4.02% reduction p≤0.001). These results suggest that zinc acetate and colchicine are potential candidates for less toxic therapies in HNC patients.