Molecular mechanisms of amygdalin as multifunctional anti-cancer drug: computational assessment

The 'cancer' is a group of biological diseases. Cancer cell switches off the apoptosis signaling, proliferate uncontrollably, resist to anticancer therapies and spread into distant organs. Therefore, controlling these three main properties by targeting key proteins can give promising strategy as anticancer. Double docking, molecular dynamics (MD) simulation, principal component analysis (PCA), free energy landscape (FEL) and binding free energy estimations (MM/PBSA) are implemented to explore the molecular basis of the biological activities of amygdalin. Amygdalin as apoptosis inducer: the docking clarifies that amygdalin binds to the interface of Bcl-2/BAX complex. The MD simulation exhibited that amygdalin causes disruption between Bcl-2/BAX. Further, FEL and PCA revealed that the Bcl-2/amygdalin is more stable than Bcl-2/BAX. In the case of caspase-3 the matter is different where amygdalin activates caspase-3 through increasing the dynamics of caspase-3. For PARP-1, amygdalin blocked PARP-1 binding pocket. Inhibition of CDK1/Cyclin B, CDK 2/Cyclin A and CDK 4/Cyclin D1 as targets for cell cycle division by amygdalin. The obtained results showed that amygdalin inhibits CDK1/Cyclin B, CDK 2/Cyclin A effectively. Targeting the metastasis, the obtained results revealed that amygdalin shows an inhibitory-metastasis activity against AKT1, FAK1 and ILK proteins. Amygdalin disclosed a clarification of the mystery amygdalin's experimental actions.