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Description
Colon cancer remains a leading cause of cancer-related mortality globally, necessitating novel therapeutic strategies. Phytochemicals such as resveratrol and genistein have garnered attention due to their potential anticancer properties, which include modulating cell growth and inducing apoptosis in various cancer models. This study aims to explore the effects of resveratrol and genistein on colon cancer cell lines, specifically focusing on the induced mutational changes and their implications for cancer therapy, using advanced next-generation sequencing (NGS) techniques.
We selected two colon cancer cell lines (HCT116 and RKO) that differ in their genetic backgrounds and mutational profiles. These cell lines were treated with resveratrol and genistein at various concentrations, individually and in combination, at 24,48 and over a 72-hour. We choose the best IC50 obtained at 24h for both cell lines and both natural compounds.
Following treatment, comprehensive genomic profiling was conducted using NGS to assess changes in the mutational status of these cell lines. We used the 50 cancer genes panel from Thermo Scientific and the experiments run into the Ion Torrent platform after nucleic acids extraction and quantification and library preparation. Our results showed that each cell line responded uniquely to the treatments, strongly influenced by their initial genetic characteristics. For instance, HCT116 cells, known for their high microsatellite instability (MSI-H), exhibited more significant apoptotic rates and extensive mutational changes, especially when exposed to both phytochemicals simultaneously. This suggests a synergistic interaction that may be pivotal in optimizing therapeutic outcomes.
The study highlights the critical role of genetic context in determining the responsiveness of colon cancer cells to treatment with natural compounds. Our findings support the potential of resveratrol and genistein as part of a targeted therapy approach, which could be tailored based on the genetic makeup of individual tumors. This personalised approach could enhance the efficacy of treatment modalities and lead to better management of colon cancer, emphasising the need for further clinical studies to validate these findings. The integration of phytochemicals with conventional therapies could potentially shift the paradigm of cancer treatment towards more specific, less toxic, and genetically informed strategies.
