Isolinderalactone Induces Apoptosis, Autophagy, Cell Cycle Arrest and MAPK Activation through ROS-Mediated Signaling in Colorectal Cancer Cell Lines.
Int J Mol Sci
; 24(18)2023 Sep 18.
Article
em En
| MEDLINE
| ID: mdl-37762548
ABSTRACT
Colorectal cancer (CRC) is one of the most common malignancies worldwide. Isolinderalactone (ILL), a sesquiterpene isolated from the root extract of Lindera aggregata, has been reported to exhibit anti-proliferative and anti-metastatic activities in various cancer cell lines. However, the mechanisms associated with its antitumor effects on CRC cells remain unclear. ILL treatment significantly suppressed proliferation and induced cell cycle G2/M arrest in CRC cells by inhibiting the expression of cyclin B, p-cdc2, and p-cdc25c and up-regulating the expression of p21. In addition, ILL induced mitochondria-associated apoptosis through the up-regulation of cleaved -caspase-9 and -3 expression. ILL induced autophagy by increasing the levels of LC3B in CRC cells, which was partially rescued by treatment with an autophagy inhibitor (chloroquine). Furthermore, ILL increases the accumulation of reactive oxygen species (ROS) and activates the MAPK pathway. Application of the ROS scavenger, N-acetyl cysteine (NAC), effectively inhibited ILL toxicity and reversed ILL-induced apoptosis, cell cycle arrest, autophagy, and ERK activation. Taken together, these results suggest that ILL induces G2/M phase arrest, apoptosis, and autophagy and activates the MAPK pathway via ROS-mediated signaling in human CRC cells.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Problema de saúde:
6_colon_rectum_cancers
Assunto principal:
Sesquiterpenos
/
Neoplasias Colorretais
Limite:
Humans
Idioma:
En
Revista:
Int J Mol Sci
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Taiwan