Identification of two small molecule inhibitors of hypoxia-inducible factor 1 with different cell-based screening model / 中国中药杂志
China Journal of Chinese Materia Medica
; (24): 2151-2155, 2012.
Artigo
em Chinês
| WPRIM (Pacífico Ocidental)
| ID: wpr-338684
Biblioteca responsável:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the inhibitory activity of HIF-1 by triptolide and manasaantin A, two cell-based models with luciferase report gene assay were established.</p><p><b>METHOD</b>Two cell-based models of HIF-1 were used to evaluate HIF-1 inhibition activity of triptolide and manasaantin A. Secreted VEGF expression induced by hypoxia was detected by ELISA with two compounds. The growth inhibition of different solid tumor cell lines was measured by the MTT assay.</p><p><b>RESULT</b>The expression of firefly luciferase was induced by hypoxia in U251-HRE and T47D-HRE cells. U251-HRE model was suitable for the detection of HIF-1 inhibition activity of triptolide. The IC50 of triptolide on HIF-1 activity was (3.4 +/- 0.5) x 10(-8) mol x L(-1). The report gene assay using T47D cells co-transfected with pGL2-TK-HRE and pRL-CMV showed more sensitive inhibition activity of HIF-1 on manassantin A than that of detected by U251-HRE model. The IC50 of manassantin A on HIF-1 activity was (2.4 +/- 0.6) x 10(-8) mol x L(-1). HIF-1 target gene VEGF was also inhibited by test compounds on protein level in T47D cells. Manasaantin A showed selective inhibition on the growth of human solid cancer cell lines, especially on breast cancer and pancreatic cancer cells. Meanwhile, triplotide showed strong proliferation inhibition activity on all tested cell lines.</p><p><b>CONCLUSION</b>It is very important to select a suitable cell-based report gene assay of HIF-1 for screening of different kinds of inhibitor.</p>
Texto completo:
Disponível
Base de dados:
WPRIM (Pacífico Ocidental)
Assunto principal:
Patologia
/
Farmacologia
/
Fenantrenos
/
Lignanas
/
Linhagem Celular Tumoral
/
Proliferação de Células
/
Diterpenos
/
Avaliação Pré-Clínica de Medicamentos
/
Tratamento Farmacológico
/
Compostos de Epóxi
Tipo de estudo:
Estudo diagnóstico
/
Estudo prognóstico
/
Estudo de rastreamento
Limite:
Humanos
Idioma:
Chinês
Revista:
China Journal of Chinese Materia Medica
Ano de publicação:
2012
Tipo de documento:
Artigo