Discovery of Palbociclib as a potent c-Myc G4 stabilizer for lung cancer treatment using molecular docking, molecular...

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Lung cancer remains a leading cause of cancer-related mortality worldwide.
• Novel therapeutic strategies are crucial to improve patient outcomes.
• Targeting oncogenic pathways like c-Myc is a promising avenue for cancer treatment.

Purpose of the Study:

• To investigate the efficacy of Palbociclib, a CDK4/6 inhibitor, in inhibiting lung cancer cell proliferation.
• To explore the potential of Palbociclib as a c-Myc G4 stabilizer.
• To elucidate the molecular mechanisms underlying Palbociclib's anti-cancer effects.

Main Methods:

• Cell viability assays (IC50 determination) in H1299 and A549 lung cancer cell lines.
• Analysis of c-Myc protein and mRNA expression levels.
• Cell cycle analysis and apoptosis assays.
• Circular dichroism (CD), molecular docking, and molecular dynamics (MD) simulations to assess G4 structure stabilization and binding affinity.

Main Results:

• Palbociclib demonstrated significant inhibition of lung cancer cell growth with IC50 values of 11.00 μM (H1299) and 11.74 μM (A549).
• Palbociclib treatment led to decreased c-Myc protein and mRNA expression.
• The drug induced apoptosis and G2/M cell cycle arrest.
• CD, docking, and MD simulations confirmed Palbociclib's ability to stabilize c-Myc G4 structures and bind effectively.

Conclusions:

• Palbociclib exhibits potent anti-cancer activity against lung cancer cells by inhibiting proliferation and inducing cell death.
• Palbociclib functions as a c-Myc G4 stabilizer, offering a novel therapeutic mechanism.
• These findings support the potential of Palbociclib as a targeted therapy for cancers with aberrant c-Myc activity, warranting further clinical investigation.