Synergistic eradicating impact of 5-fluouracil with FeO nanoparticles-diethyldithiocarbamate in colon cancer spheroids

<b>Background: </b>Cancer stem cells’ (CSCs) resistance to 5-fluorouracil (Fu), which is the main obstacle in treating colon cancer (CC), can be overcome by ferroptosis. The latter, herein, can be triggered by FeO nanoparticles (inducer of iron accumulation) and diethyldithiocarbamate-inhibited glutathione system and aldehyde dehydrogenase (ALDH1A1-maintained stemness, therapeutic resistance and metastasis). <b>Materials &amp; methods: </b>Nanocomplex of FeO nanoparticles and diethyldithiocarbamate (FD) was used in combination with Fu to investigate its potential synergistic anti-CSC influence using CC spheroid models. <b>Results: </b>In Fu <b>+ </b>FD-treated spheroids, the strongest growth inhibition, the highest cell death percentage, and the lowest CD133<b>+</b>-CSCs percentage and stemness gene expressions (e.g., drug efflux transporter), and the strongest antimetastatic effect were recorded with high synergistic indexes. <b>Conclusion: </b>Fu <b>+ </b>FD represents effective combination therapy for chemoresistant CC cells.