Controlling non small cell lung cancer progression by blocking focal adhesion kinase-c-Src active site with Rosmarinus officinalis L. phytocomponents: An in silico and in vitro study.

Abstract

Non small cell lung cancer (NSCLC) is a global, fatal oncological malady to which conventional and targeted therapies proved less effective with consequent side effects; hence, phytocomponents from herbal sources may provide potent alternative and should be tested for cancer intervention. Activation and overexpression of proto-oncogene tyrosine kinase Src (c-Src) and focal adhesion kinase (FAK) lead to cell proliferation and invasion. Hence, in the present investigation, in silico analysis was carried out to identify molecular intervention of phytocomponents in blocking the active site and thus inhibiting c-Src and FAK activation, which in turn could control progression of NSCLC. In silico analysis was carried out using Molegro Virtual Docker, Molegro Molecular Viewer, and ClusPro server for ligand-protein and protein-protein interaction study. Phytochemical analysis and assay for antioxidant activity of hydroalcoholic extract of Rosmarinus officinalis L. were carried out using standard phytochemical tests, high-performance thin-layer chromatography, and 2, 2-diphenyl-1-picrylhydrazyl assay. Effectiveness of extract in arresting cell proliferation was confirmed using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay on A549 cell line. In silico analysis indicated effective binding of rosmarinic acid to the active site of target proteins FAK and c-Src, blocking their activity. MTT assay revealed potent antiproliferative activity of hydroalcoholic extract which acted in dose-dependent manner. Phytochemical analysis confirmed that the extract was rich in phytocomponents and had antioxidant activity of 94.9%, which could therefore effectively eliminate free radicals and inhibit cell progression. In silico and in vitro studies confirmed that phytocomponents present in hydroalcoholic extract of R. officinalis L. could effectively block the active site of target proteins and thus controlled cell proliferation on NSCLC cells, suggesting herb as an effective alternative medicine for the treatment of NSCLC.