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

Area of Science:

• Biochemistry
• Molecular Biology
• Computational Chemistry

Background:

• Curcumin (CUR) is investigated for its anticancer properties.
• Targeted drug delivery and protein interactions are crucial in cancer therapy.
• Folate receptors play a role in cellular uptake.

Purpose of the Study:

• To explore the therapeutic potential of curcumin in cancer therapy.
• To investigate curcumin's interaction with specific proteins in breast cancer cell lines.
• To assess the binding affinity and stability of curcumin-protein complexes.

Main Methods:

• Molecular docking was used to assess binding affinities of CUR with proteins 1H1Q, 1UOM, 4JDD, 5U2D, and a normal breast epithelial cell line protein (5UGB).
• Molecular dynamics simulations (100 ns) were performed on the most stable complex (CUR-1H1Q) to evaluate its biological stability.
• Cytotoxicity and biocompatibility were assessed in both normal and cancerous breast cell lines (MCF7, MCF10A).

Main Results:

• The CUR-1H1Q complex exhibited the highest binding affinity among tested proteins.
• Molecular dynamics simulations confirmed the stability of the CUR-1H1Q complex, showing a stable Cα-backbone, consistent hydrogen bonding, and a condensed structure.
• Curcumin demonstrated enhanced biocompatibility and selective toxicity towards cancerous cell lines (MCF7) compared to normal cell lines (MCF10A), with protein 1H1Q significantly influencing its cytotoxicity.

Conclusions:

• Curcumin's interaction with specific proteins, particularly 1H1Q, is a key factor in its anticancer activity against breast cancer cells.
• The stable complex formation between curcumin and 1H1Q suggests a mechanism for inducing cancer cell death.
• Curcumin exhibits favorable biocompatibility and selective toxicity, highlighting its potential as a targeted cancer therapeutic.