Reversal of multidrug resistance and antitumor promoting activity of 3-oxo-6β-hydroxy-β-amyrin isolated from Pistacia integerrima

摘要

The bioactive triterpenoid 3-oxo-6-β-hydroxy-β-amyrin(1)has been isolated from multiple plant sources.In this study,chloroform fraction of Pistacia integerrima extract was processed for the isolation of the compound.The compound identity was confirmed by advanced spectroscopy technique.X-ray crystallography was applied for molecular structure confirmation.In addition,compound 1 was screen for its activity on reversal of MDR(multidrug resistance)mediated by P-gp(P-glycoprotein).This was accomplished by using rhodamine123 exclusion on multidrug-resistant human ABCB1 gene transfected mouse T-lymphoma cell line.Outcomes revealed that MDR reversing effect was comparable to verapamil as positive control in vitro.Treatment of TPA-induced tumor promotion with 3-oxo-6β-hydroxy-β-amyrin led to reduction in the applied anti-tumor promotion experiment.The chemo-preventive effect of 3-oxo-6β-hydroxy-β-amyrin was comparable to curcumin as positive control based on the reduction of immediate early tumor antigen expression.Molecular docking by applying Autodock Vina 1 and i-GEMDOCK v 2.1 tools indicated that compound 1 gives good docking results,as determined by their fitness score and specificity.Moreover,results showed that compound 1 isolated from Pistacia integerrima precisely attached to a region where co-crystallized ligand for receptor previously existed.Our findings may explain the use of Pistacia integerrima plant extracts as an anticancer agent in folk medicine.