Cytotoxicity of Moringa oleifera fruits on human liver cancer and molecular docking analysis of bioactive constituents against caspase-3 enzyme

Moringa oleifera is an excellent source of phenolics and flavonoids comprise various pharmacological activities. The fourth widespread leading cause of the patients' death is liver cancer. This study was formulated to perform the antiproliferative activity of Moringa oleifera fruit (MOF) extract on human liver cancer HepG2 cells and computational validation of cell death. HepG2 cell line was treated with 25, 50, 75, 100, and 200 mu g/ml of MOF extract for 48 hr, and antiproliferative activity was analyzed using MTT assay, nuclear condensation, annexin V-FITC/PI double stain, ROS generation, and apoptosis executioner enzyme caspase-3. MOF extract reduced the cell viability significantly (p < .05) by increasing cellular apoptosis which was confirmed by annexin V-FITC/PI staining assay. In addition, MOF stimulated intracellular ROS production and subsequently induced caspase-3 activity depending upon dose. In silico analysis revealed the good binding interaction between amino acid residues of caspase-3 (PDB ID: 1GFW) protein and selected active constituents of MOF. PASS analyses of the phytoconstituents showed no violation of Lipinski's rule of five. Analysis of drug-likeness and toxicity measurement exhibited drug-like candidates with no predicted toxicity. In conclusion, this study showed the potential anticancer activity of MOF extract which may be valuable source for anticancer drug development. Practical applications Moringa oleifera fruit extract induced the anti-proliferative activity against human hepatocellular carcinoma HepG2 cells through ROS-mediated apoptosis and activation of caspase-3 enzyme. Structure-based virtual screening study between bioactive components of Moringa oleifera fruits and apoptosis executioner caspase-3 enzyme has validated the anti-proliferative activity of Moringa oleifera fruit extract. Interestingly, active phytoconstituents of Moringa oleifera fruit exhibited drug-like candidates with no predicted toxicity. Thus, Moringa oleifera fruit could be used as valuable source for anticancer drug development against human liver cancer with relatively non-toxic to healthy cells.