Curcumin as an Antitumor Agent: Targeting Cancer Stem Cell Markers in Glioblastoma through In Silico and In Vitro Approaches

Glioblastoma is prevalent and aggressive primary malignant brain tumor in adults with an annual incidence rate approximately 0.59 to 5 cases per 100,000 individuals. Curcumin, a bioactive compound from Curcuma longa, holds promise as a potential antitumor agent for use in drug or functional food development. This study aimed to analyze the in silico and in vitro antitumor potency of curcumin. Molecular docking was conducted to assess curcumin’s interactions with tumor-related proteins SOX-2, OCT-4, and IGFBP2. In vitro experiments involved quantifying the SOX-2 and OCT-4 genes expression in glioblastoma (GBM) cells treated with curcumin using qRT-PCR method. Molecular docking revealed that curcumin binds effectively to all target proteins, with SOX-2 and OCT-4 exhibiting the lowest binding energy also the highest number of interactions, indicating stronger binding. In vitro analysis demonstrated that curcumin significantly downregulated the SOX-2 and OCT-4 expression in GBM cells, surpassing the effects of temozolomide, a standard cancer treatment. These findings highlight curcumin's potential as an antitumor agent by targeting cancer stem cell markers and pathways. This study provides foundational evidence for the future development of curcumin-based drugs or functional foods aimed at cancer therapy. HIGHLIGHTS Curcumin effectively binds to cancer stem cell markers such as SOX-2, OCT-4, and IGFBP2 as evidenced by molecular docking with strong binding affinity and multiple protein-ligand interactions. Curcumin significantly downregulates the SOX-2 and OCT-4 gene expression in glioblastoma cells, surpassing the effects of temozolomide, the current standard chemotherapeutic. The findings highlight curcumin's role in inhibiting cancer stemness and reducing tumor aggressiveness, providing a foundation for its development into curcumin-based functional foods or drugs for cancer therapy. GRAPHICAL ABSTRACT