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1.
Biomolecules ; 9(12)2019 11 21.
Artículo en Inglés | MEDLINE | ID: mdl-31766534

RESUMEN

Inflammatory bowel disease (IBD) is general term for ulcerative colitis and Crohn's disease, which is chronic intestinal and colorectal inflammation caused by microbial infiltration or immunocyte attack. IBD is not curable, and is highly susceptible to develop into colorectal cancer. Finding agents to alleviate these symptoms, as well as any progression of IBD, is a critical effort. This study evaluates the anti-inflammation and anti-tumor activity of 16-hydroxycleroda-3,13-dien-15,16-olide (HCD) in in vivo and in vitro assays. The result of an IBD mouse model induced using intraperitoneal chemical azoxymethane (AOM)/dextran sodium sulfate (DSS) injection showed that intraperitoneal HCD adminstration could ameliorate the inflammatory symptoms of IBD mice. In the in vitro assay, cytotoxic characteristics and retained signaling pathways of HCD treatment were analyzed by MTT assay, cell cycle analysis, and Western blotting. From cell viability determination, the IC50 of HCD in Caco-2 was significantly lower in 2.30 µM at 48 h when compared to 5-fluorouracil (5-FU) (66.79 µM). By cell cycle and Western blotting analysis, the cell death characteristics of HCD treatment in Caco-2 exhibited the involvement of extrinsic and intrinsic pathways in cell death, for which intrinsic apoptosis was predominantly activated via the reduction in growth factor signaling. These potential treatments against colon cancer demonstrate that HCD could provide a promising adjuvant as an alternative medicine in combating colorectal cancer and IBD.


Asunto(s)
Apoptosis , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Diterpenos de Tipo Clerodano/uso terapéutico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Animales , Apoptosis/efectos de los fármacos , Azoximetano , Biomarcadores de Tumor/metabolismo , Células CACO-2 , Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Sulfato de Dextran , Diterpenos de Tipo Clerodano/farmacología , Fluorouracilo/farmacología , Fluorouracilo/uso terapéutico , Células HT29 , Humanos , Inflamación/tratamiento farmacológico , Inflamación/patología , Intestinos/patología , Masculino , Ratones Endogámicos C57BL
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