Molecular landscape of THEDES selective toxicity towards colorectal cancer

Abstract

Abstract In the relentless pursuit of overcoming modern medicine most highly demanding challenges, such as the most incident and deadliest cancers, as colon and rectum cancer (CRC), we keep on seeking innovative therapeutic solutions. Following deep eutectic systems spotlight due to their remarkable physicochemical and biological properties, versatility, and compliance with the green chemistry metrics, we sought to fill the gap between the reported promising toxicity of THEDES, combining a terpene with Ibu, towards cancer cells and the understanding of their specific impact on these cells molecular landscape. Hence, an integrated approach considering the effect of combining a terpene with Ibu as a THEDES, on permeability, cellular transport, cell viability, reactive oxygen species, cell metabolome and an in vivo systemic toxicity preliminary assessment was considered. On one hand, it was observed that exposing normal colonic cells to THEDES, at their EC50, promoted Ibu transcellular transport and cellular uptake. On the other hand, from THEDES exposure, CRC cells experience a control of ROS production, cell dead induction via apoptosis, and alteration on their metabolite landscape with deleterious effect on essential metabolic pathways, as lipid and anaerobic glycolysis energy production pathways. Furthermore, from a preliminary systemic toxicity evaluation, it was observed non-relevant systemic toxicity of these THEDES within the tested concentration range.