Intestinal metabolite xylulose inhibits colorectal cancer by inducing apoptosis through the MAPK signalling pathway.
Toxicol Appl Pharmacol
; 487: 116960, 2024 Jun.
Article
en En
| MEDLINE
| ID: mdl-38735592
ABSTRACT
BACKGROUND:
The intestinal metabolites are involved in the initiation, progression and metastasis of colorectal cancer (CRC). They are a potential source of agents for cancer therapy. Our previous study identified altered faecal metabolites between CRC patients and healthy volunteers. However, no specific metabolite was clearly illustrated for CRC therapy.RESULTS:
We found that the level of xylulose was lower in the stools of CRC patients than in those of healthy volunteers. Xylulose inhibited cell growth without affecting the cell cycle by inducing apoptosis in CRC cells, which was evidenced by increased expression of the proapoptotic proteins C-PARP and C-Caspase3 and decreased expression of the antiapoptotic protein BCL-2 in CRC cells. Mechanistically, xylulose reduced the activity of the MAPK signalling pathway, represented by reduced phosphorylation of JNK, ERK, and P38. Furthermore, an ALI model was used to show the tumour killing ability of xylulose on human CRC spheres, as well as human colorectal adenoma (AD) spheres.CONCLUSION:
Xylulose inhibits CRC growth by inducing apoptosis through attenuation of the MAPK signalling pathway. These results suggest that xylulose may serve as an effective agent for CRC therapy.Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Xilulosa
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Neoplasias Colorrectales
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Apoptosis
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Sistema de Señalización de MAP Quinasas
Idioma:
En
Revista:
Toxicol Appl Pharmacol
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Toxicol. appl. pharmacol
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Toxicology and applied pharmacology
Año:
2024
Tipo del documento:
Article