Document Detail


Casearin X exhibits cytotoxic effects in leukemia cells triggered by apoptosis.
MedLine Citation:
PMID:  20816779     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Clerodane diterpenes have demonstrated cytotoxic, antiplasmodial and anti-ulcer properties. In the present work, we determined the cytotoxic effect of casearin L (Cas L), O (Cas O) and X (Cas X) and (-)-hardwickiic acid isolated from Casearia sylvestris leaves, and investigated the underlying mechanisms involved in in vitro cell death induced by Cas X in HL-60 leukemia cells (0.7, 1.5 and 3.0μM). Cytotoxicity tests demonstrated that Cas X was the most active compound studied, showing greater cytotoxic effects against CEM and HL-60 lines (IC(50) of 0.4μM) and human peripheral blood mononuclear cells (PBMC, IC(50) of 1.2μM). After 24h exposure, Cas X caused a decrease in 5-bromo-20-deoxyuridine (BrdU) incorporation (36.6 and 24.5% labeling at 0.7 and 1.5μM, respectively), reduction in viability, and increase in apoptotic and necrotic leukemia cells in a dose-dependent manner evidenced by the trypan blue and AO/EB (acridine orange/ethidium bromide) assays. Moreover, Cas X-treated cells exhibited nuclear fragmentation and cytoplasmic vacuolization depending on the concentration tested. These characteristics of apoptosis or secondary necrosis were confirmed by flow cytometry which revealed DNA fragmentation, phosphatidylserine externalization, activation of the effector caspases 3/7 and mitochondrial depolarization. We then found evidence that Cas X causes cell death via apoptotic pathways, corroborating the potential of casearins as compounds with promising antitumor-related properties.
Authors:
Paulo M Pinheiro Ferreira; André G Santos; Aristeu G Tininis; Patricia M Costa; Alberto J Cavalheiro; Vanderlan S Bolzani; Manoel O Moraes; Letícia V Costa-Lotufo; Raquel C Montenegro; Cláudia Pessoa
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Chemico-biological interactions     Volume:  188     ISSN:  1872-7786     ISO Abbreviation:  Chem. Biol. Interact.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-12     Completed Date:  2010-12-21     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0227276     Medline TA:  Chem Biol Interact     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  497-504     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
Affiliation:
Universidade Federal do Piauí, 64.600-000 Picos, Piauí, Brazil.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects*
Caspase 3 / metabolism
Caspase 7 / metabolism
Cell Membrane / drug effects,  metabolism
Cell Survival / drug effects
DNA / biosynthesis,  genetics
DNA Fragmentation / drug effects
Diterpenes / pharmacology
Diterpenes, Clerodane / pharmacology*
Enzyme Activation / drug effects
Flow Cytometry
HL-60 Cells
Humans
Leukemia / pathology*
Mitochondria / drug effects
Phosphatidylserines / metabolism
Chemical
Reg. No./Substance:
0/1-(acetyloxy)-3,5,6,6a,7,8,9,10-octahydro-10-hydroxy-7,8-dimethyl-7-(3-methylpenta-2,4-dien-1-yl)naphtho(1,8a-c)furan-3,5-diyl dibutanoate; 0/Diterpenes; 0/Diterpenes, Clerodane; 0/Phosphatidylserines; 24470-47-1/hardwickic acid; 9007-49-2/DNA; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 7

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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