Document Detail

Casearin X exhibits cytotoxic effects in leukemia cells triggered by apoptosis.
MedLine Citation:
PMID:  20816779     Owner:  NLM     Status:  MEDLINE    
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.
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
Related Documents :
2199089 - The effects of new cytochalasins from phomopsis sp. and the derivatives on cellular str...
9787069 - Sublethal damage during cryopreservation of rainbow trout sperm
20102369 - Antiproliferative activity of purine nucleoside phosphorylase multisubstrate analogue i...
19752719 - Role of efflux pump activity in lapatinib/caelyx combination in breast cancer cell lines.
20138029 - Cytotoxic activity of naphthoquinones with special emphasis on juglone and its 5-o-meth...
11299749 - Cell-specific enhancement of doxorubicin toxicity in human tumour cells by docosahexaen...
1891779 - 2,4-dichlorophenoxyacetic acid effects on polyamine biosynthesis.
9359859 - Expression of menkes disease gene in mammary carcinoma cells.
12466889 - Long anchor using flo1 protein enhances reactivity of cell surface-displayed glucoamyla...
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.
Universidade Federal do Piauí, 64.600-000 Picos, Piauí, Brazil.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
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
Leukemia / pathology*
Mitochondria / drug effects
Phosphatidylserines / metabolism
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

Previous Document:  Anti-inflammatory effects of dietary phenolic compounds in an in vitro model of inflamed human intes...
Next Document:  Publisher's Note.