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Biomed Pharmacother ; 63(2): 146-54, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18450412

RESUMO

The commercially available analogue of indirubin, indirubin-3-oxime, is known for its antitumor activities. To further establish its role in anticancer activity, we tested its potential against human laryngeal carcinoma cell line (Hep-2). We investigated the molecular mechanisms of indirubin-induced apoptosis and growth arrest in human laryngeal carcinoma cells. Upon treatment with indirubin-3-monooxime, a time dependent inhibition of cell growth was observed and cells developed many hallmark features of apoptosis. The increase of chromatin condensation after treatment with indirubin-3-oxime identified by staining with chromatin stain Hoechst 333258 indicates apoptosis. The observed increase in DNA fragmentation after indirubin-3-oxime in DNA gel electrophoresis indicates the apoptotic feature exhibited by the drug. Flow cytometric analysis confirmed that indirubin increased populations of apoptotic phase G1. Indirubin-3-oxime-induced growth inhibition was associated with induction of Cdk inhibitor p21, inhibition of cyclin D1 and activation of caspase-3. We conclude that indirubin-3-oxime induces cell death and apoptosis in human laryngeal carcinoma cells.


Assuntos
Antineoplásicos/farmacologia , Indóis/farmacologia , Neoplasias Laríngeas/tratamento farmacológico , Oximas/farmacologia , Apoptose/efeitos dos fármacos , Caspase 3/efeitos dos fármacos , Caspase 3/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cromatina/efeitos dos fármacos , Cromatina/metabolismo , Ciclina D1/antagonistas & inibidores , Inibidor de Quinase Dependente de Ciclina p21/efeitos dos fármacos , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Fragmentação do DNA/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Eletroforese em Gel de Ágar , Citometria de Fluxo , Humanos , Neoplasias Laríngeas/patologia , Fatores de Tempo
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