Abstract
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.
Highlights
Pistacia integerrima is a well-known member of family Anacardiaceae family, which is commonly known as Kakar sigghi in Eastern Himalayan (Ismail et al, 2011), at an altitude of 2.4 to 3.6 km
Spectral data employed that the chemical structure of 1 (Fig. 1) has been identified as 3-oxo-6β-hydroxy-β-amyrin
Its effect on multidrug resistance (MDR) mouse lymphoma cell line was evaluated, results of which are displayed in Tab. 3
Summary
The most important difficulty in chemotherapy and in the cure of cancer are the resistance pattern of cancer cells knowns as multidrug resistance (MDR) (Szabó and Molnar, 2016). The resistance of Cancer cells to anticancer agents is developed through several mechanisms One of such mechanisms is the overexpression of the ATP-binding cassette (ABC) transporters. In several human cancers the overexpression of this protein occurs and can eject a wideranging of drugs, i.e., antibiotics, anticancer, antidepressants, and others (Caraci et al, 2011) It decreases drug accumulation in multidrug-resistant cells. Pistacia integerrima is a well-known member of family Anacardiaceae family, which is commonly known as Kakar sigghi in Eastern Himalayan (Ismail et al, 2011), at an altitude of 2.4 to 3.6 km This is a medium sized deciduous plant with folkloric health modulating importance for a number of ailments. The current finding was performed to discover the reversal ability of the isolated compound for multidrug-resistance in mouse lymphoma cells
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