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




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BMC Complementary and Alternative Medicine

, 13:286

Basic research

Abstract

BackgroundBioactivity-guided fractionation of extracts of Aglaia loheri Blanco Meliaceae yielded a cytotoxic isolate, termed Maldi 531.2M + 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 531.2M + H. XTT cell proliferation and viability assay was used for cytotoxic test, and JC-15’,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 531.2M + 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 531.2M + H may be a potential anti-cancer drug candidate whose mode of action include reduction of the mitochondrial membrane potential and induction of apoptosis.

KeywordsAglaia loheri Cytotoxicity Multi-drug resistance Apoptosis JC-1 mitochondrial membrane potential Annexin V-FITC AbbreviationsALLAcute lymphoblastic leukemia

CCCPCarbonyl cyanide 3-chlorophenylhydrazone

CCRF-CEMSensitive human leukemia cells

CEM-ADR5000Multidrug resistant leukemia cells

CFColumn fractions

EAEEthyl acetate extract

ECEEthanolic concentrated extract

HCT116Human Colon cancer cell line

HEHexane extract

HPLCHigh liquid performace chromatography

MDPMaster dilution plate

MTT3-4,5-dimethylthiazol-2-yl2,5-diphenyltetrazolium bromide

NMRNuclear magnetic resonance

PBMCPeripheral blood mononuclear cells

PHAPhytohemagglutinin

PIPropidium ioodide

PSPhosphatidylserine

SFSub-fractions of CF

TLCThin layer chromatography

XTT2,3-bis2-methoxy-4-nitro-5-sulfophenyl-2H-tetrazolium-5-carboxalnilide.

Sonia Jacinto and Thomas Efferth contributed equally to this work.

Electronic supplementary materialThe online version of this article doi:10.1186-1472-6882-13-286 contains supplementary material, which is available to authorized users.

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Autor: Else Dapat - Sonia Jacinto - Thomas Efferth

Fuente: https://link.springer.com/



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