Evaluation of Selected Natural Compounds for Cancer Stem Cells Targeted Anti-cancer Activity: A Molecular Docking Study

Abstract

Aims: Cancer stem cells (CSCs) play significant roles in tumor initiation, relapse, angiogenesis, metastasis and therapy. Collectively Wnt, Notch, and Hedgehog are major pathways that have been linked to the drug resistance of CSCs. Eliminating CSCs has been suggested as a promising approach to cure cancer. Aim of the present study is screening of selected natural compounds for inhibitors of Wnt, and Hedgehog pathways that have been linked to the drug resistance of cancer stem cells (CSCs) by in silico molecular docking analysis. Methodology: In the present study, in silico molecular docking simulations were carried out for the binding of 35 selected natural compounds with receptor proteins which are involved in the main signaling pathways of CSCs, such as β-catenin chain A and Smo receptor from the Wnt and hedgehog pathways respectively, using Hex 8.0.0, DOCK6 and AutoDock Vina software. Docking interaction residue analysis, score functions and drug-likeness studies were carried out for the selected compounds. Results: Overall, 11 compounds such as Gedunin, Kaempferol, Methylripariochromene A, Myrigalone G, Catechin, Myricetin, Discretine, Laurolitsine, Myricitrin, Nordicentrine and Phloretin were identified with good binding energy, interaction, binding affinity and better drug likeness for β-catenin chain A. There was no considerable overall binding ability for Smo inhibition. Conclusion: Our results demonstrate that 11 compounds out of 35 natural compounds screened can be used for further development of CSC targeted anti-cancer drugs. In vitro studies need to be carried out to confirm anti-CSC activity of the novel inhibitors discovered.