RESUMEN

STAT3 signaling pathway is an important target for human cancer therapy. Thus, the identification of small-molecules that target STAT3 signaling will be of great interests in the development of anticancer agents. The aim of this study was to identify novel inhibitors of STAT3 pathway from the roots of Zanthoxylum nitidum (Roxb.) DC. The bioassay-guided fractionation of MeOH extract of Z. nitidum using a STAT3-responsive gene reporter assay led to the isolation of angoline (1) as a potent and selective inhibitor of the STAT3 signaling pathway (IC50=11.56 µM). Angoline inhibited STAT3 phosphorylation and its target gene expression and consequently induced growth inhibition of human cancer cells with constitutively activated STAT3 (IC50=3.14-4.72 µM). This work provided a novel lead for the development of anti-cancer agents targeting the STAT3 signaling pathway.

Asunto(s)

Antineoplásicos Fitogénicos/farmacología , Fenantridinas/farmacología , Extractos Vegetales/farmacología , Transducción de Señal/efectos de los fármacos , Zanthoxylum/química , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Genes Reporteros , Células Hep G2 , Humanos , Concentración 50 Inhibidora , Interleucina-6/genética , Interleucina-6/metabolismo , Fenantridinas/química , Fenantridinas/aislamiento & purificación , Fosforilación/efectos de los fármacos , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Raíces de Plantas/química , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo