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Biomolecules ; 9(12)2019 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-31766534

RESUMO

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.


Assuntos
Apoptose , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Diterpenos Clerodânicos/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Azoximetano , Biomarcadores Tumorais/metabolismo , Células CACO-2 , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sulfato de Dextrana , Diterpenos Clerodânicos/farmacologia , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Células HT29 , Humanos , Inflamação/tratamento farmacológico , Inflamação/patologia , Intestinos/patologia , Masculino , Camundongos Endogâmicos C57BL
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