Toxicogenomic evaluation of the combination of nutraceuticals in human colorectal adenocarcinoma cell lines

Abstract

Colorectal cancer (CCR) is the second type of cancer with higher mortality and high incidence rates in recent decades. The development of adverse effects and drug resistance necessitates the need to develop alternative treatments to traditional therapy. One of the treatments is the use of nutraceuticals, compounds present in natural products that regulate various metabolic pathways and can modulate multiple biomarkers in cancer cells, reducing their viability. The use of nutraceuticals aims to reduce the doses of conventional chemotherapy administered to patients, thereby decreasing their adverse effects and resistance. Among the existing nutraceuticals, this study aims to investigate, individually and in combination, the action of three compounds that have individually shown efficacy in controlling cancer cells: vitamin D, caffeic acid, and diallyl disulfide. The in vitro model of CCR will be employed using the HT-29 and Caco-2 cell lines and the non-tumoral human colon fibroblast cell line (CCD-18Co). The methods to be used will include cytotoxicity assays (using resazurin and fluorescent dyes), genotoxicity assays (comet assay), apoptosis assays by flow cytometry, cell migration, redox state change analysis, Western blotting for analysis of DNA methylation proteins expression, and quantification of global DNA methylation. The potential synergistic effect of the combination of these nutraceuticals represents an important research target for the development of alternative therapies in the treatment of colorectal cancer.