Abstract
Interaction of vincamine docked with the caspase-3. The ligand, vincamine, has been shown in ‘green-stick’ representation.
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•Vincamine demonstrates as anti-cancer agent against human alveolar basal epithelial cell line.•DCFH-DA, DAPI, mitochondrial membrane potential, caspase-3 inhibition assessed.•In-silico studies shows anti-proliferative potential by interaction with anti-apoptotic protein.•Vincamine quench hydroxyl free radicals and deplete iron ion concentration in the cancer cells.•Being a food additive, vincamine found almost nontoxic against 3T3-L1 cells.
Vincamine, a well-known plant alkaloid, has been used as a dietary supplement and as a peripheral vasodilator to combat aging in humans. In this study, for the very first time, we demonstrated that vincamine can function as an anticancer agent in a human alveolar basal epithelial cell line A549 (IC50 = 309.7 μM). The anticancer potential of vincamine in A549 cells was assessed by molecular assays to determine cell viability, generation of intracellular ROS, nuclear condensation, caspase-3 activity and inhibition, and change in mitochondrial membrane potential (ΔΨm). In silico studies predicted that the anti-proliferative potential of vincamine is enhanced by its interaction with the apoptotic protein caspase-3, and that this interaction is driven by two hydrogen bonds and has a high free energy of binding (−5.64 kcal/mol) with an estimated association constant (Ka) of 73.67 μM. We found that vincamine stimulated caspase-3-dependent apoptosis and lowered mitochondrial membrane potential, which ultimately led to cytochrome C release. Vincamine was also found to quench hydroxyl free radicals and deplete iron ions in cancer cells. As a dietary supplement, vincamine is almost non-toxic in BEAS-2B and 3T3-L1 cells. Therefore, we propose that vincamine represents a safe anticancer agent in lung cancer cells. Its role in other cancers has yet to be explored.