title: A phenolic ester from Aglaia loheri leaves reveals cytotoxicity towards sensitive and multidrug-resistant cancer cells.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biology, University of the Philippines, Manila City, Philippines. elsegdapat40@gmail.com.
authors.forename: Else
authors.initials: E
authors.lastname: Dapat
authors.forename: Sonia
authors.initials: S
authors.lastname: Jacinto
authors.forename: Thomas
authors.initials: T
authors.lastname: Efferth
mesh_terms: D031602:Aglaia / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001205:Ascorbic Acid / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000503:physiopathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010636:Phenols / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D010636:Phenols; D010936:Plant Extracts; C069207:calcium ascorbate; D001205:Ascorbic Acid