Derivate isocorydine inhibits cell proliferation in hepatocellular carcinoma cell lines by inducing G2/M cell cycle arrest and apoptosis.
Tumour Biol
; 37(5): 5951-61, 2016 May.
Article
in En
| MEDLINE
| ID: mdl-26596832
ABSTRACT
We have previously demonstrated that isocorydine (ICD) can be served as a potential antitumor agent in hepatocellular carcinoma (HCC). A novel derivate of isocorydine (d-ICD) could significantly improve its anticancer activity in tumors. However, the molecular mechanisms of d-ICD on HCC cells remain to be unclear. In this study, we observed that d-ICD inhibited cell proliferation and induced apoptosis of HCC cells in a concentration-dependent manner. We found d-ICD induced G2/M cycle arrest of HCC cells via DNA damage 45 alpha (GADD45A) and p21 pathway in vitro and in vivo. In d-ICD-treated cells, cell cycle-related proteins cyclin B1 and p-CDC2 were upregulated and p-cyclin B1, CDC2, and E2F1 were inhibited. p21 expression can be reversed by knockdown of GADD45A in d-ICD-treated HCC cells. Enforced expression of CCAAT/enhancer-binding protein ß (C/EBPß) in combination with d-ICD enhanced the p21 expression in HCC cells. Furthermore, the luciferase reporter assay showed that upregulation of GADD45A by C/EBPß was achieved through the increase of GADD45A promoter activity. These findings indicate that d-ICD inhibits cell proliferation and induces cell cycle arrest through activation of C/EBPß-GADD45A-p21 pathway in HCC cells. d-ICD might be a promising chemotherapeutic agent for the treatment of HCC.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Aporphines
/
Antineoplastic Agents, Phytogenic
Type of study:
Prognostic_studies
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Tumour Biol
Journal subject:
NEOPLASIAS
Year:
2016
Document type:
Article
Affiliation country: