Structural analysis of cannabinoids against EGFR-TK leads a novel target against EGFR-driven cell lines

Area of Science:

• Oncology
• Pharmacology
• Molecular Biology

Background:

• Epidermal growth factor receptor (EGFR) is crucial for cell growth and proliferation, and its overexpression is linked to cancer progression.
• Targeting EGFR is a key strategy in cancer drug development.
• Cannabis-derived compounds (cannabinoids) exhibit various medicinal properties, including antitumor effects, but their mechanism against EGFR signaling is not fully understood.

Purpose of the Study:

• To investigate the potential of cannabinoids (CBD, CBG, CBN) to inhibit EGFR signaling.
• To evaluate the binding affinity and mode of these cannabinoids to the EGFR intracellular domain using molecular docking simulations.

Main Methods:

• Molecular docking simulations were employed to assess the binding of CBD, CBG, and CBN to the EGFR kinase active site.
• Binding energy and mode were analyzed.
• In vitro assays were conducted to evaluate the compounds' effects on EGFR-overexpressing cancer cell lines.

Main Results:

• Cannabinoids demonstrated favorable binding at the EGFR kinase active site.
• The tested compounds exhibited significant binding affinity, indicating potential kinase inhibition.
• CBD, CBG, and CBN potently inhibited cellular survival and induced apoptosis in EGFR-overexpressing cell lines.

Conclusions:

• Cannabinoids show promise as inhibitors of EGFR signaling.
• These findings support the therapeutic potential of cannabinoids in treating cancers characterized by EGFR overexpression.
• Further research into cannabinoid-based EGFR inhibitors is warranted.