Pharmacokinetic properties and anti-proliferative mechanisms of vanillin against acute lymphoblastic leukemia (Jurkat) cells

Abstract

The anti-proliferative potential of vanillin isolated from an ethnomedicine Flacourtia indica bark was evaluated in an acute lymphoblastic leukemia cell line (Jurkat) in our previous study, but its molecular mechanisms of action are not yet revealed. The present work investigated the pharmacokinetic properties & cellular uptake of vanillin, in addition to evaluating the effect of vanillin treatment on cell morphology, mitochondrial membrane potential, DNA fragmentation, and cell survival & pro-apoptotic proteins in Jurkat cells. High absorption, good oral bioavailability, and safety of vanillin were recorded through in silico pharmacokinetic studies. In vitro study results indicate that 24.07% of vanillin was absorbed by Jurkat cells within 120 min. The IC50 dose of vanillin reduced the mitochondrial membrane potential up to 77.05% and also caused 60.94% of DNA fragmentation in Jurkat cells. Further, inhibition of cell survival proteins such as H-RAS, K-RAS, N-RAS, & BCL-2 and activation of pro-apoptotic proteins like p-38, BAX, pro-caspase-9, pro-caspase-3, and caspase-3 by vanillin was confirmed through molecular docking and western blotting studies. Thus, the current study revealed the pharmacokinetic properties and anti-proliferative mechanisms of vanillin in Jurkat cells. Therefore vanillin could be further investigated to develop a safe and alternative phytopharmaceutical to treat acute lymphoblastic leukemia.