Impact of curcumin on ferroptosis-related genes in colorectal cancer: Insights from in-silico and in-vitro studies

Colorectal cancer (CRC) is responsible for a significant number of cancer-related fatalities worldwide. Researchers are investigating the therapeutic potential of ferroptosis, a type of iron-dependent controlled cell death, in the context of CRC. Curcumin, a natural compound found in turmeric, exhibits anticancer properties. This study explores the effects of curcumin on genes related to ferroptosis (FRGs) in CRC. To gather CRC data, we used the Gene Expression Profiling Interactive Analysis (GEPIA) and Gene Expression Omnibus (GEO) databases, while FRGs were obtained from the FerrDb database and PubMed. We identified 739 CRC differentially expressed genes (DEGs) in CRC and discovered 39 genes that were common genes between FRGs and CRC DEGs. The DEGs related to ferroptosis were enriched with various biological processes and molecular functions, including the regulation of signal transduction and glucose metabolism. Using the Drug Gene Interaction Database (DGIdb), we predicted drugs targeting CRC-DEGs and identified 17 potential drug targets. Additionally, we identified eight essential proteins related to ferroptosis in CRC, including MYC, IL1B, and SLC1A5. Survival analysis revealed that alterations in gene expression of CDC25A, DDR2, FABP4, IL1B, SNCA, and TFAM were associated with prognosis in CRC patients. In SW480 human CRC cells, treatment with curcumin decreased the expression of MYC, IL1B, and EZH2 mRNA, while simultaneously increasing the expression of SLCA5 and CAV1. The findings of this study suggest that curcumin could regulate FRGs in CRC and have the potential to be utilized as a therapeutic agent for treating CRC. The application of bioinformatic tools for finding dysregulated genes in cancer is a new applicable approach in finding new therapies for cancers. Ferroptosis as a nonapoptotic form of cell death is involved in numerous biological and pathological cellular process in cancers. Also, the antiapoptotic properties of curcumin as a polyphenol with anti-inflammatory properties and the ability to increase the amount of antioxidants in cells, are under deep investigation in cancer therapy. Herein, we investigated the effects of curcumin on ferroptosis-related genes (FRGs) in colorectal cancer (CRC). The results of in-silico and in-vitro studies indicated that curcumin could regulate FRGs in CRC and has a potential to be a new therapeutic agent for ferroptosis- resistance CRC.