A phenolic ester from Aglaia loheri leaves reveals cytotoxicity towards sensitive and multidrug-resistant cancer cells

Abstract

Doc number: 286

Abstract

Background: Bioactivity-guided fractionation of extracts of Aglaia loheri Blanco (Meliaceae) yielded a cytotoxic isolate, termed Maldi 531.2[M + H]⁺ . This phenolic ester was further investigated for its in vitro cytotoxicity toward human CCRF-CEM leukemia cells and their multi-drug resistant (MDR) subline, CEM/ADR5000. The intrinsic mitochondrial membrane potential (ΔΨm) and induction of apoptosis by this isolate were evaluated.

Methods: Chromatography techniques, mass spectrometry and proton NMR were employed to isolate Maldi 531.2[M + H]⁺ . XTT cell proliferation and viability assay was used for cytotoxic test, and JC-1[5',5',6,6',-tetrachloro-1,1',3,3'-tetraethylbenzimidazoyl carbocyanine iodide was used to assess ΔΨm and initiation of apoptosis; Annexin V/FITC-PI staining was employed to analyse apoptosis.

Results: Maldi 531.2[M + H]⁺ was cytotoxic towards both CCRF-CEM and CEM/ADR5000 cells with IC₅₀ values of 0.02 and 0.03 μM, respectively. The mitochondrial membrane potential (ΔΨm) of MDR cells was significantly reduced in a dose-dependent manner leading to apoptosis as detected by flow cytometric Annexin V-FITC/ PI staining.

Conclusion: Maldi 531.2[M + H]⁺ may be a potential anti-cancer drug candidate whose mode of action include reduction of the mitochondrial membrane potential and induction of apoptosis.