Abstract
•Controlling the molar ratio of choline to geranic acid in a choline and geranic acid (CAGE) deep eutectic solvent (DES) led to anticancer properties.•CAGE DES reduced the viability of skin cancer cells without harming normal cells.•CAGE DES did not trigger the expression of biomarkers of inflammation.•CAGE DES did not rupture the cell membrane but increased oxidative stress on cancer cells.•CAGE had the potential for application in anti-squamous cell carcinoma chemotherapy.
The properties of deep eutectic solvents (DESs) are tunable, providing a route to new functions. Choline and geranic acid (CAGE) class of DESs shows antimicrobial properties, acts as drug delivery systems, and functions as anti-obesity agents. We hypothesize that new properties are attainable by rational variation of the molar ratios of choline and geranic acid. This study assessed the anticancer properties of a series of CAGE DESs, aiming to develop novel topical chemotherapy for squamous cell carcinoma of the skin. Cell viability assay demonstrated that varying the molar ratio of choline and geranic acid provided a strategy to significantly reduce the viability of human squamous carcinoma of the skin cell line (A431) without compromising the viability of human normal skin fibroblast cell line (CRL-2091). This molar ratio did not induce CRL-2091 to release interleukin–1β (IL–1β), a biomarker of acute and chronic inflammation, suggesting that the therapeutic dose of CAGE is unlikely to trigger skin inflammation. The anticancer property of CAGE is attributable to geranic acid, which also reduced the viability of A431 and CRL-2091 cell lines. With regards to mechanism, the therapeutic dose of CAGE did not rupture the cell membrane but induced oxidative stress on the A431 cell line. Concluding, rationally varying choline and geranic acid molar ratios provides a strategy to endow new properties on CAGE as demonstrated by selective activity against squamous cell carcinoma of the skin.
