An In Vitro, In silico, GCMS and LCMS Investigation of Crinum jagus (J. Thomp.) Dandy Bulb for Lead Anti-Hepatocellular Carcinoma Compounds

Abstract

Hepatocellular carcinoma is a leading cause of cancer-related death around the world. In this study, the 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay was used to investigate the anticancer activity of five chromatographic fractions of Crinum jagus methanol bulb extract against the hepatocellular carcinoma (HepG2) cell line. The IC50 value was used as a measure of anticancer activity. The most active fraction was analyzed using GCMS and LCMS. The binding energies of the identified compounds with Caspase-3, Caspase-9 and EGFR were evaluated and compared with that of the standard drug, Sorafenib. The compounds' drug-likeness was evaluated by applying Lipinski's rule of five. The IC50 value of the most active fraction was 37 μg/ml. Nineteen (19) compounds, primarily fatty acids, fatty acid esters, and flavonoids, were identified from the fraction by GCMS and LCMS analysis. Of the nineteen (19) compounds identified in the most active fraction, linoelaidic acid (-8.23 kcal mol-1), hexadecanoic acid (-7.96 kcal mol-1) and 9,12-Octadecadienoic acid (-7.78 kcal mol-1) had better binding affinity for Caspase-3 than Sorafenib; hexadecanoic acid methyl ester (-8.10 kcal mol-1) and pentyl linoleate (-8.00 kcal mol-1) had comparable binding energy with Sorafenib (-8.47 kcal mol-1) against Caspase-9; while hexadecanoic acid (-8.29 kcal mol-1), linoelaidic acid (-8.58 kcal mol-1), and pentyl linoleate (-8.66 kcal mol-1) had better binding energy than Sorafenib (-8.24 kcal mol-1) against EGFR. These compounds passed Lipinski’s test for drug-likeness. The study's findings lend credence to the plant's traditional use as a cancer remedy.