Bioinformatic analysis of the molecular targets of curcumin in colorectal cancer

Pathol Res Pract. 2024 Oct:262:155533. doi: 10.1016/j.prp.2024.155533. Epub 2024 Aug 11.

Abstract

Colorectal cancer (CRC) is a major global health concern, with rising incidence and mortality rates. Conventional treatments often come with significant complications, prompting the exploration of natural compounds like curcumin as potential therapeutic agents. Using bioinformatic tools, this study investigated the role of curcumin in CRC treatment. Significant protein interactions between curcumin and target proteins were identified in the STITCH database. Differentially expressed genes (DEGs) associated with CRC were then analyzed from GEO databases. Comparing curcumin targets and CRC-related DEGs, nine significant common targets were identified: DNMT1, PCNA, CCND1, PLAU, MMP3, SOX9, FOXM1, CXCL2, and SERPINB5. Pathway enrichment analyses revealed that curcumin-targeted pathways were primarily related to p53, IL-17, NF-kappa B, TNF, and cell cycle signaling, all crucial in CRC development and progression. Further analyses using DAID and EnrichR algorithms showed that the curcumin targets exhibited greater specificity to bronchial epithelial cells and colorectal adenocarcinoma than other diseases. Analyses via the DSigDB database indicated that curcumin ranks highly among other drugs targeting the identified CRC-related genes. Docking studies revealed favorable binding interactions between curcumin and the key CRC-related proteins, suggesting potential molecular mechanisms by which curcumin may exert its effects. In summary, this study provides bioinformatic and docking evidence that curcumin may exert beneficial effects on CRC by modulating the expression or activity of multiple CRC-susceptibility genes involved in critical signaling pathways. These findings warrant further experimental validation and support the potential of curcumin as a therapeutic agent for CRC.

Keywords: Bioinformatics; Colorectal cancer; Curcumin; Gene Ontology; KEGG.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / metabolism
  • Colorectal Neoplasms* / pathology
  • Computational Biology* / methods
  • Curcumin* / pharmacology
  • Curcumin* / therapeutic use
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Molecular Docking Simulation
  • Protein Interaction Maps / drug effects
  • Signal Transduction / drug effects

Substances

  • Curcumin
  • Antineoplastic Agents