Study on the Inhibitory Effect of Curcumin on GBM and Its Potential Mechanism

Drug Des Devel Ther. 2021 Jun 28:15:2769-2781. doi: 10.2147/DDDT.S306602. eCollection 2021.

Abstract

Background: Glioblastoma (GBM) is the most prevalent malignant tumor of the central nervous system (CNS). However, current GBM treatments are ineffective, signifying the great importance of exploring new therapeutic targets. Curcumin has been found to be a natural compound with an anticancer potential. However, its targets and mechanisms in GBM are still unclear.

Methods: Differentially expressed genes (DEGs) were screened from the GBM dataset in the GEO database and intersected with the target genes of curcumin to select potential target genes. Subsequently, survival analysis was performed with the GEPIA database to confirm the effect of target genes on the prognosis of GBM, and functional enrichment analysis was performed using the DAVID database. In vitro, CCK-8 assay was used to screen the appropriate concentration of curcumin; scratch and transwell invasion assays were used to evaluate the effect of curcumin on the migration and invasion abilities of GBM cells. Furthermore, RT-qPCR and Western blotting were used to detect changes in target genes and flow cytometry was used to assess the apoptosis level.

Results: A total of 16 target genes of curcumin and GBM were obtained, among which ENO1, MMP2, and PRKD2 significantly affected the prognosis (P < 0.05). We further selected ENO1 for functional enrichment analysis and found that it was enriched in the glycolytic pathway. Meanwhile, in vitro experiments showed that curcumin could inhibit the migration and invasion of U251 cells and promote apoptosis (P < 0.05).

Conclusion: ENO1 could be a possible target for curcumin in the suppression of GBM cells.

Keywords: ENO1; apoptosis; computational biology; curcumin; glioblastoma; migration.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Biomarkers, Tumor / genetics
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Curcumin / pharmacology*
  • DNA-Binding Proteins / genetics
  • Gene Expression Regulation, Neoplastic
  • Glioblastoma / drug therapy*
  • Glioblastoma / genetics
  • Glioblastoma / pathology
  • Humans
  • Neoplasm Invasiveness / prevention & control
  • Phosphopyruvate Hydratase / genetics
  • Tumor Suppressor Proteins / genetics

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Tumor Suppressor Proteins
  • ENO1 protein, human
  • Phosphopyruvate Hydratase
  • Curcumin

Grants and funding

This work was supported by The National Natural Science Foundation of China (No. 81860222) and the Science and Technology Plan Project of Guangxi (No. AB16380204).