Exploration of Allium ascalonicum L for Anticancer Properties using in silico in vitro and in vivo Lung Cancer Models

Abstract

The present study was conducted to evaluate the anticancer potential of A. ascalonicum using newlinein silico, in vitro and in vivo models. The study was conducted in four distinct phases. In phase I, newlinephytochemical parameters and free radical scavenging activity of different extracts of A. ascalonicum newlinewere analysed. In phase II, lead compounds against lung cancer target proteins were identified from newlinethe secondary active constituents of A. ascalonicum using ligand based docking. In phase III, in vitro newlineanticancer potential of Allicin a compound present in A. ascalonicum was assessed using human lung newlinecancer cell line, A549. In the final phase of the study, in vivo investigations on impact of Allicin on newlinebenzopyrene induced lung tumour bearing Swiss albino mice were carried out. newlineQualitative phytochemical analysis of different solvents (ethanol, chloroform, methanol, water) newlinerevealed the presence of seven major phytoconstituents namely alkaloids, carbohydrates, flavonoids, newlinetannins, glycosides, terpenoids and phenols. Among the four solvents, maximum intensity of newlinephytochemicals was reported in methanol extract. Free radical scavenging activities of these extracts newlinewere determined in vitro against a variety of radicals namely DPPH, FRAP, H2O2 and reducing power newlineassay. The highest scavenging efficacy of DPPH, FRAP and hydrogen peroxide were 80.67%, 77.12% newlineand 80.88% respectively at 40 and#956;g/mL. newlineThe methanol extract was subjected to GC-MS and the chemical constituents identified newlinepredominantly in the extract were further subjected to molecular docking analysis against lung cancer newlineproteins by using Auto dock 4.2.8. Among the compounds, Allicin was the most potent against the newlinetarget cancer protein, as evidenced by highest docking score. newlineThe antiproliferative indices of A549 cells showed a dose dependent decrease in cell viability newlinewith IC50 values of Allicin 28 and#956;M. The effect of Allicin on the regulation of protein expression and newlineapoptotic gene expression revealed the up regulation of different proteins including Caspase-3, p53, newlineCytochrom