Abstract

Cancer stem cells (CSCs) play significant roles in tumor initiation, tumor relapse, angiogenesis, and metastasis and therapy resistance. CSC theory concerning the commonality of deregulation of three crucial pathways; Wnt, notch and hedgehog that maintain CSC’s self-renewal capacity is emerging. Collectively these major pathways have been linked to the observed resistance of CSCs to conventional therapy. Most therapies are directed at the rapid growing tumor mass but not at the slow dividing CSCs. Eliminating CSCs, the root of cancer origin and recurrence has been thought as a promising approach to cure cancer. Therefore, in-silico analysis is used to recognize anticancer compounds as a future prospective for in-vitro and in-vivo analysis of the activity of anticancer compounds. In the present study the Wnt and hedgehog pathways and their receptors which can bind to natural compounds are focused on.

Molecular docking simulations were carried out for the binding of selected natural compounds with receptor proteins which are involved in main signaling pathways of CSCs, such as β-catenin chain A and Smo receptor from the Wnt and hedgehog pathways respectively. Additionally docking interaction residue analysis, score function and drug-likeness study were carried out for selected compounds. Based on these final results, Gedunin, Kaempferol, Methylripariochromene A, Myrigalone G, Catechin, Myricetin, Discretine, Laurolitsine, Myricitrin, Nordicentrine and Phloretin were identified as novel natural compounds for Wnt inhibition. Finally, the novel inhibitors proposed in the present study could be studied further to discover potential cancer treatment with the generated pharmacophore model and thus interrupt the Wnt signaling pathway in CSCs.

Keywords

Cancer stem cells

Introduction