Metabolic profiling of Lagunaria patersonii leaves extract in relation to its cytotoxic activity: in vitro and in silico studies

Lagunaria patersonii (Andrews) G. Don. leaves were studied for their cytotoxic activity in relation to phytoconstituents on different tumor cell lines. The fractions prepared from the total alcoholic extract: n-hexane (Hex.), dichloromethane (DCM), ethyl acetate (EtOAc), and butanol (BuOH) were evaluated on three human cancer cell lines: Caco-2, MCF7, and PC3, using MTT assay. Both Hex and DCM showed strong cytotoxic activity against PC3 cells and moderate cytotoxic activity against Caco-2 and MCF7 cell lines. Thus, the fluorescent staining and immunofluorescence techniques were used to determine the effects of Hex and DCM fractions on cell death and the anti-apoptotic protein (BCL-2) expression in PC3 cells. The predominant mode of cell death was late apoptosis. Meanwhile, there was a significant decrease in BCL-2 protein expression in both Hex and DCM-treated cells compared to untreated control cells. The two bioactive fractions were screened for their phytoconstituents using UHPLC-QTOF-MS/MS where 22 compounds were tentatively identified. In addition, the Hex fraction was examined using GLC for its lipid content. 33 fatty acids were detected in the saponifiable fraction, while 19 compounds were detected in the unsaponifiable fraction. The isolated bioactive compounds from the two fractions were identified as 24-methylene-3, 4-seco-cycloart-4(28)-en-3-oic acid, triolein, and stigmasterol. A molecular docking study on BCL-2 target receptor revealed that the isolated compounds demonstrated high binding scores, particularly triolein, which surpassed the co-crystallized ligand. This strongly suggests the significant apoptotic potential of the examined candidates derived from Lagunaria patersonii (Andrews) G. Don leaves.