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

BMC Complementary and Alternative Medicine

Thomas Efferth²  Sonia Jacinto¹  Else Dapat² 

[1] Institute of Biology, University of the Philippines, Diliman, Quezon City, Philippines;German Cancer Research Center, Heidelberg, Germany

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

Others  :  1220870
DOI  :  10.1186/1472-6882-13-286

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

【 摘 要 】

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.

【 授权许可】

   
2013 Dapat et al.; licensee BioMed Central Ltd.

【 图 表 】

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