Silymarin induces inhibition of growth and apoptosis through modulation of the MAPK signaling pathway in AGS human gastric cancer cells.
Oncol Rep
; 42(5): 1904-1914, 2019 Nov.
Article
em En
| MEDLINE
| ID: mdl-31485597
ABSTRACT
Apoptosis is regarded as a therapeutic target because it is typically disturbed in human cancer. Silymarin from milk thistle (Silybum marianum) has been reported to exhibit anticancer properties via regulation of apoptosis as well as antiinflammatory, antioxidant and hepatoprotective effects. In the present study, the effects of silymarin on the inhibition of proliferation and apoptosis were examined in human gastric cancer cells. The viability of AGS human gastric cancer cells was assessed by MTT assay. The migration of AGS cells was investigated by wound healing assay. Silymarin was revealed to significantly decrease viability and migration of AGS cells in a concentrationdependent manner. In addition, the number of apoptotic bodies and the rate of apoptosis were increased in a dosedependent manner as determined by DAPI staining and Annexin V/propidium iodide double staining. The changes in the expression of silymarininduced apoptosis proteins were investigated in human gastric cancer cells by western blotting analysis. Silymarin increased the expression of Bax, phosphorylated (p)JNK and pp38, and cleaved polyADP ribose polymerase, and decreased the levels of Bcl2 and pERK1/2 in a concentrationdependent manner. The in vivo tumor growth inhibitory effect of silymarin was investigated. Silymarin (100 mg/kg) significantly decreased the AGS tumor volume and increased apoptosis, as assessed by the TUNEL assay, confirming its tumorinhibitory effect. Immunohistochemical staining revealed elevated expression of pJNK and pp38 as well as reduced expression of pERK1/2 associated with silymarintreatment. Silymarin was revealed to reduce tumor growth through inhibition of pERK and activation of pp38 and pJNK in human gastric cancer cells. These results indicated that silymarin has potential for development as a cancer therapeutic due to its growth inhibitory effects and induction of apoptosis in human gastric cancer cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Silimarina
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Neoplasias Gástricas
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Sistema de Sinalização das MAP Quinases
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Antineoplásicos Fitogênicos
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article