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.

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.

• Authors: Else Dapat, Sonia Jacinto, Thomas Efferth
• Journal: BMC complementary and alternative medicine (BMC Complement Altern Med) Vol. 13 Pg. 286 (Oct 27 2013) ISSN: 1472-6882 [Electronic] England
• PMID: 24160768 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Phenols
• Plant Extracts
• calcium ascorbate
• Ascorbic Acid

Topics

• Aglaia (chemistry)
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Ascorbic Acid (pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Drug Resistance, Neoplasm
• Humans
• Leukemia (drug therapy, physiopathology)
• Membrane Potential, Mitochondrial (drug effects)
• Phenols (pharmacology)
• Plant Extracts (pharmacology)