Probiotic-based derived exopolysaccharide-zinc oxide nanoparticles: a novel approach to colorectal cancer gene modulation

Bioorg Chem. 2025 Oct:165:109025. doi: 10.1016/j.bioorg.2025.109025. Epub 2025 Sep 29.

Abstract

The second deadliest cancer in the world is colorectal cancer (CRC), which is caused by the uncontrolled proliferation of epithelial cells in the colon. This research examines the role of key genes-including tumor suppressors ING4 and APC, angiogenesis-related DHX32, and the oncogenic mutated P53-in the SW480 cell line. Probiotics and their exopolysaccharide (EPS) component show potential in cancer prevention and treatment due to their antioxidant and anti-cancer properties. Zinc oxide nanoparticles (ZnONPs), recognized for their unique physical and chemical characteristics, have broad applications in drug delivery, cancer diagnostics, and therapy. In this project, EPS was extracted from Lactiplantibacillus plantarum and used for ZnONPs biosynthesis, followed by characterization through UV-VIS, XRD, FTIR, FE-SEM, and zeta potential analysis. Cytotoxic effects of EPS and ZnONPs were evaluated on SW480 cells, along with their antioxidant properties. Quantitative real-time PCR analysis revealed decreased expression of DHX32 and P53, while ING4 and APC gene expression increased following treatment of the cancerous cell line with target agents. These findings suggest that probiotic-derived EPS and ZnONPs may offer effective strategies for CRC treatment by modulating critical gene expression involved in disease progression.

Keywords: Angiogenesis; Colorectal cancer; Exopolysaccharide; Probiotics; Tumor suppressor and oncogenic genes; Zinc oxide nanoparticles.

MeSH terms

  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Antioxidants / chemistry
  • Antioxidants / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / pathology
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Structure
  • Nanoparticles* / chemistry
  • Particle Size
  • Polysaccharides, Bacterial* / chemistry
  • Polysaccharides, Bacterial* / isolation & purification
  • Polysaccharides, Bacterial* / pharmacology
  • Probiotics* / chemistry
  • Probiotics* / pharmacology
  • Structure-Activity Relationship
  • Zinc Oxide* / chemistry
  • Zinc Oxide* / pharmacology

Substances

  • Polysaccharides, Bacterial
  • Zinc Oxide
  • Antineoplastic Agents
  • Antioxidants