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

作者：Dapat Else^*; Jacinto Sonia; Efferth Thomas

来源：BMC Complementary and Alternative Medicine, 2013, 13: 286.

DOI：10.1186/1472-6882-13-286

• Aglaia loheri
• Cytotoxicity
• Multi-drug resistance
• Apoptosis
• JC-1 mitochondrial membrane potential
• Annexin V-FITC

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 (Delta psi m) 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 Delta psi m 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 mu M, respectively. The mitochondrial membrane potential (Delta psi m) 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.

• 出版日期2013-10-27