Osthole induced apoptosis in human normal liver cells by regulating cell proliferation and endoplasmic reticulum stress.
Environ Toxicol
; 34(6): 768-776, 2019 Jun.
Article
em En
| MEDLINE
| ID: mdl-30848542
ABSTRACT
Osthole (Ost) is often used in treatment for cancer, inflammation and rheumatism in clinic. However, Ost-induced liver injury has been reported. In this study, we aim to investigate the possible mechanism of Ost-induced hepatotoxicity in human normal liver cells (L02). When cells were exposed to Ost, the cell viability was decreased and apoptosis rate increased, the intracellular markers of oxidative stress were changed. Simultaneously, Ost altered apoptotic related proteins levels, including Bcl-2, Bax, Cleaved-Caspase-9/-8/-3, and Pro-Caspase-3/-8. In addition, Ost enhanced the levels of endoplasmic reticulum (ER) stress proteins (GRP78/Bip, CHOP, Caspase-4, IRE1α, PERK, JNK, P-JNK, and ATF4), decreased the cell proliferation and cycle-associated protein (Phospho-Histone H3, P-Cdc25C, Cdc25C, P-Cdc2, Cdc2, and Cyclin B1) level. The results show that Ost has toxic effects on L02 cells. Furthermore, it induces apoptosis by inhibiting cell proliferation, arresting cell cycle at the G2/M phase and activating ER stress.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Apoptose
/
Cumarínicos
/
Proliferação de Células
/
Estresse do Retículo Endoplasmático
/
Fígado
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article