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

BMC Complementary and Alternative Medicine

Research Article

Else Dapat¹  Thomas Efferth²  Sonia Jacinto³ 

[1] Department of Biology, University of the Philippines, Manila City, Philippines;Institute of Biology, University of the Philippines, Diliman, Quezon City, Philippines;German Cancer Research Center, Heidelberg, Germany;Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Guttenberg University, Mainz, Germany;German Cancer Research Center, Heidelberg, Germany;Institute of Biology, University of the Philippines, Diliman, Quezon City, Philippines;

关键词: Aglaia loheri;    Cytotoxicity;    Multi-drug resistance;    Apoptosis;    JC-1 mitochondrial membrane potential;    Annexin V-FITC;   

DOI  :  10.1186/1472-6882-13-286

 received in 2012-12-09, accepted in 2013-10-25,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundBioactivity-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.MethodsChromatography 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.ResultsMaldi 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.ConclusionMaldi 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.

【 授权许可】

CC BY   
© Dapat et al.; licensee BioMed Central Ltd. 2013