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1.
Journal of Experimental Hematology ; (6): 975-978, 2005.
Artigo em Chinês | WPRIM | ID: wpr-343845

RESUMO

The retinoid N-4-hydroxyphenyl retinamide (4-HPR also known as fenretinide), a synthetic derivative of all trans retinoic acid (ATRA), has shown as an efficient chemopreventive, chemotherapeutic agent and a potent inducer of apoptosis in various cancer cell types in vitro, including leukemic cells. However the mechanisms by which 4-HPR has the apoptotic effects is not completely elucidated. This study was aimed to investigate the effect of 4-HPR on several leukemic cells and explore its mechanisms of effect on U937 cells. The cell growth and proliferation experiments were performed [corrected] cell apoptosis was detected by annexin V; reactive oxygen species (ROS) and mitochondrial transmembrane potential (DeltaPsim) were determined; protein [corrected] expression was detected by Western blot. The results showed that 4-HPR inhibited the proliferation of U937 cells in a dose- and time-dependent manner. 4-HPR markedly [corrected] induced apoptosis in U937 cells, triggered the generation of ROS, induced the loss of mitochondrial transmembrane potential, decreased the expression of procaspase-8 and procaspase-3. Pretreatment of L-ascorbic acid suppressed the generation of ROS, disruption of mitochondrial potential, activation of caspases and apoptosis. It is concluded that the generation of ROS followed by the disruption of mitochondrial transmembrane potential plays an important role on 4-HPR-induced apoptosis in leukemic cells, suggesting that 4-HPR may be one of mitochondrial-targeted agents with clinical potential in treating cancer.


Assuntos
Humanos , Antineoplásicos , Farmacologia , Apoptose , Western Blotting , Caspases , Metabolismo , Relação Dose-Resposta a Droga , Fenretinida , Farmacologia , Células HL-60 , Células K562 , Leucemia , Metabolismo , Patologia , Potencial da Membrana Mitocondrial , Espécies Reativas de Oxigênio , Metabolismo , Células U937
2.
Chinese Journal of Medical Genetics ; (6): 422-425, 2004.
Artigo em Chinês | WPRIM | ID: wpr-328859

RESUMO

<p><b>OBJECTIVE</b>To get an insight into the molecular mechanisms of diseases development and targeted therapy at the transcriptome level and search for potential therapeutic targets.</p><p><b>METHODS</b>The present researchers established a cDNA microarray platform and applied component plane presentation integrated self-organizing map (CPP-SOM) to the microarray data obtained from a differentiation model, all trans retinoic acid-induced differentiation in NB4 cells.</p><p><b>RESULTS</b>The platform included 12630 unique clones, including 9436 known genes. By CPP-SOM, the researchers were able to not only well classify the regulated genes into functionally distinct categories but also depict transcriptional changes throughout the process of the development of diseases or drug treatment.</p><p><b>CONCLUSION</b>The platform has proven to be steady and reliable, and the CPP-SOM could serve as an important and good tool for analysis of microarray data.</p>


Assuntos
Humanos , Linhagem Celular Tumoral , Análise de Sequência com Séries de Oligonucleotídeos , Métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa
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