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Biochem Biophys Res Commun ; 425(3): 613-8, 2012 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-22877755

RESUMO

Despite the improved contemporary multidisciplinary regimens treating cancer, majority of cancer patients still suffer from adverse effects and relapse, therefore posing a significant challenge to uncover more efficacious molecular therapeutics targeting signaling pathways central to tumorigenesis. Here, our study have demonstrated that Triparanol, a cholesterol synthesis inhibitor, can block proliferation and induce apoptosis in multiple human cancer cells including lung, breast, liver, pancreatic, prostate cancer and melanoma cells, and growth inhibition can be rescued by exogenous addition of cholesterol. Remarkably, we have proved Triparanol can significantly repress Hedgehog pathway signaling in these human cancer cells. Furthermore, study in a mouse xenograft model of human lung cancer has validated that Triparanol can impede tumor growth in vivo. We have therefore uncovered Triparanol as potential new cancer therapeutic in treating multiple types of human cancers with deregulated Hedgehog signaling.


Assuntos
Antineoplásicos/uso terapêutico , Proteínas Hedgehog/antagonistas & inibidores , Hipolipemiantes/uso terapêutico , Neoplasias/tratamento farmacológico , Triparanol/uso terapêutico , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Hipolipemiantes/química , Hipolipemiantes/farmacologia , Camundongos , Camundongos Nus , Triparanol/química , Triparanol/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
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