Cafestol inhibits colon cancer cell proliferation and tumor growth in xenograft mice by activating LKB1/AMPK/ULK1-dependent autophagy.
J Nutr Biochem
; 129: 109623, 2024 Jul.
Article
en En
| MEDLINE
| ID: mdl-38492819
ABSTRACT
Chemotherapy failure in colorectal cancer patients is the major cause of recurrence and poor prognosis. As a result, there is an urgent need to develop drugs that have a good chemotherapy effect while also being extremely safe. In this study, we found cafestol inhibited colon cancer growth and HCT116 proliferation in vivo and in vitro, and improved the composition of intestinal flora. Further metabolomic data showed that autophagy and AMPK pathways were involved in the process of cafestol's anti-colon cancer effects. The functional validation studies revealed that cafestol increased autophagy vesicles and LC3B-II levels. The autophagic flux induced by cafestol was prevented by using BafA1. The autophagy inhibitor 3-MA blocked the cafestol-induced increase in LC3B-II and cell proliferation inhibition. Then we found that cafestol induced the increased expressions of LKB1, AMPK, ULK1, p-LKB1, p-AMPK, and p-ULK1 proteins in vivo and in vitro. Using the siRNA targeted to the Lkb1 gene, the levels of AMPK, ULK1, and LC3B-II were suppressed under cafestol treatment. These results indicated that the effect of cafestol is through regulating LKB1/AMPK/ULK1 pathway-mediated autophagic death. Finally, a correlation matrix of the microbiome and autophagy-related proteins was conducted. We found that cafestol-induced autophagic protein expression was positively correlated with the beneficial intestinal bacteria (Muribaculaceae, Bacteroides, Prevotellacece, and Alloprevotella) and negatively correlated with the hazardous bacteria. Conclusions:
This study found that cafestol inhibited colon cancer in vitro and in vivo by the mechanism that may be related to LKB1/AMPK/ULK1 pathway-mediated autophagic cell death and improved intestinal microenvironment.Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Autofagia
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Proteínas Serina-Treonina Quinasas
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Neoplasias del Colon
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Proliferación Celular
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Diterpenos
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Proteínas Quinasas Activadas por AMP
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Homólogo de la Proteína 1 Relacionada con la Autofagia
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
J Nutr Biochem
/
J. nutr. biochem
/
Journal of nutritional biochemistry
Asunto de la revista:
BIOQUIMICA
/
CIENCIAS DA NUTRICAO
Año:
2024
Tipo del documento:
Article