RESUMO
The leaves of Artocarpus tonkinensis are used in Vietnamese traditional medicine for treatment of arthritis, and the compound maesopsin 4-O-ß-D-glucoside (TAT-2), isolated from them, inhibits the proliferation of activated T cells. Our goal was to test the anti-proliferative activity of TAT-2 on the T-cell leukemia, Jurkat, and on the acute myeloid leukemia, OCI-AML. TAT-2 inhibited the growth of OCI-AML (and additional acute myeloid leukemia cells) but not Jurkat cells. Growth inhibition was shown to be due to inhibition of proliferation rather than increase in cell death. Analysis of cytokine release showed that TAT-2 stimulated the release of TGF-ß, yet TGF-ß neutralization did not reverse the maesopsin-dependent effect. Gene expression profiling determined that maesopsin modulated 19 identifiable genes. Transcription factor CP2 was the gene most significantly modulated. Real-time PCR validated that up-regulation of sulphiredoxin 1 homolog (SRXN1), hemeoxygenase 1 (HMOX1), and breast carcinoma amplified sequence 3 (BCAS3) were consistently modulated.
Assuntos
Benzofuranos/farmacologia , Glucosídeos/farmacologia , Heme Oxigenase-1/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Proteínas de Neoplasias/genética , Oxirredutases atuantes sobre Doadores de Grupo Enxofre/genética , Artocarpus/química , Morte Celular/efeitos dos fármacos , Processos de Crescimento Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/genética , Relação Dose-Resposta a Droga , Expressão Gênica/efeitos dos fármacos , Perfilação da Expressão Gênica/métodos , Células HL-60 , Heme Oxigenase-1/biossíntese , Humanos , Células Jurkat , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Leucemia de Células T/tratamento farmacológico , Leucemia de Células T/genética , Leucemia de Células T/metabolismo , Leucemia de Células T/patologia , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/biossíntese , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Oxirredutases atuantes sobre Doadores de Grupo Enxofre/biossíntese , Linfócitos T/efeitos dos fármacos , Fatores de Transcrição/genética , Fator de Crescimento Transformador beta/metabolismo , Células U937 , Regulação para Cima/efeitos dos fármacosRESUMO
Activity-guided fractionation of the n-butanol extract from the leaves of Artocarpus tonkinensis led to the isolation of the auronol glycosides maesopsin 4-O-glucoside (1), as well as the new alphitonin-4-O-glucoside (2). These structures were identified on the basis of MS and NMR spectroscopic data. The lymphocyte stimulation test showed both compounds having immunosuppressive activity.
