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Mol Med Rep ; 17(3): 3527-3536, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29286105

RESUMO

The roots of Codonopsis cordifolioidea (classified as campanulaceae cordifolioidea), locally known as Tsoong, have been used as a tonic food. The major components isolated from Tsoong have been demonstrated to present anti­human immunodeficiency virus­1 activities and cytotoxicity against various tumor cell lines. However, the possible effects of the novel compound isolated from Tsoong, cordifoliketones A, on pancreatic ductal adenocarcinoma (PDAC) cells, are still unknown. In the present study, cordifoliketones A extractions were prepared from Tsoong, and the possible effects on PDAC cell growth, apoptosis, migration and invasion in vitro and in vivo were exlored. The cytotoxicity assay, apoptosis assay, western blotting, migration and invasion assay, and a PDAC cell (AsPC­1, BxPC­3 and PANC­1) xenograft mice model were employed. The results demonstrated that treatment with cordifoliketones A: i) inhibited proliferation and promoted apoptosis of PDAC cells; ii) significantly induced apoptosis and altered expression of apoptosis­associated proteins in a dose­dependent manner; iii) suppressed migration and invasion of PDAC cells in a dose­dependent manner; and iv) restrained the growth of PDAC neoplasm in nude mice. Furthermore, cordifoliketones A demonstrated non­cytotoxic activity in a panel of normal human cells, including hTERT­HPNE, 293, hepatocyte HL­7702 and HL­1 cells. Therefore, these data indicated that cordifoliketones A may be a potential candidate compound for the prevention of PDAC cell proliferation and metastasis, presumably by induction apoptosis and inhibiting viability, invasion and migration of PDAC cells.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Codonopsis/química , Fenilpropionatos/farmacologia , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/uso terapêutico , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patologia , Caspases/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Codonopsis/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Fenilpropionatos/química , Fenilpropionatos/uso terapêutico , Extratos Vegetais/química , Raízes de Plantas/química , Raízes de Plantas/metabolismo , Transplante Heterólogo
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