In Silico Analysis of Curcumin's Targeted Cancer Therapy: Folate Receptor Pathways and Molecular Interaction Insights

Abstract

This study explores the therapeutic potential of curcumin (CUR) in cancer therapy, specifically examining its targeted transport through folate receptors and its interaction with certain proteins in breast cancer cell lines. We employed molecular docking technique to assess the binding affinities of CUR with proteins 1H1Q, 1UOM, 4JDD, 5U2D and MCF10A normal breast epithelial cell line protein 5UGB. Out of these, the CUR-1H1Q complex exhibited the greatest binding affinity. To assess the stability of this complex in a biological setting, we conducted molecular dynamics simulations of the 1H1Q-CUR complex for a duration of 100 ns. The simulations demonstrated an extremely stable Cα-backbone, exhibiting a consistently low root mean square deviation. The radius of gyration measurements suggested a condensed structure with specific areas of flexibility. The simulation revealed a consistent hydrogen bond between CUR and 1H1Q, indicating a robust and long-lasting interaction between the two molecules. The results indicate that the cytotoxicity of curcumin on MCF7 cancer cell lines is mainly affected by its interactions with several proteins found in these cancer cells. Among the four proteins tested, 1H1Q has the greatest influence. The high affinity of these proteins for curcumin, which results in the creation of stable complexes, seems to trigger cell death. Curcumin's biocompatibility and toxicological effects were investigated in both normal and cancerous cell lines. The study revealed enhanced biocompatibility and potential toxicity in cancerous cell lines, while demonstrating reduced toxicity in normal cell lines.

Keywords: Cancer therapy; Curcumin; Folate receptor; Molecular docking; Molecular dynamics; Targeted drug delivery.