4.3 Article

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

Journal

BIOCELL
Volume 45, Issue 1, Pages 139-147

Publisher

TECH SCIENCE PRESS
DOI: 10.32604/biocell.2021.013277

Keywords

Pistacia integerrima; Anti-tumor properties; X-ray crystallography; POM; Molecular docking

Categories

Funding

  1. Higher Education commission, Pakistan (HEC) [NRPU649]

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The bioactive triterpenoid 3-oxo-6-beta-hydroxy-beta-amyrin has been isolated from Pistacia integerrima and shown to have potential for reversing multidrug resistance and inhibiting tumor promotion. Molecular docking analysis indicated good interaction of the compound with target receptors, supporting its use as a potential anticancer agent.
The bioactive triterpenoid 3-oxo-6-beta-hydroxy-beta-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-6 beta-hydroxy- beta-amyrin led to reduction in the applied anti-tumor promotion experiment. The chemo-preventive effect of 3-oxo-6 beta-hydroxy- beta-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.

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