Differentiative pathway activated by 3-aminobenzamide, an inhibitor of PARP, in human osteosarcoma MG-63 cells.
FEBS Lett
; 579(3): 615-20, 2005 Jan 31.
Article
in En
| MEDLINE
| ID: mdl-15670817
ABSTRACT
This study describes the molecular mechanism by which treatment with 3-AB, a potent inhibitor of PARP, allows human osteosarcoma MG-63 cells to restrict growth and enter differentiation. Our findings show that in MG-63 cells, aberrant gene expression keeps Rb protein constitutively inactivated through hyperphosphorylation and this promotes uncontrolled proliferation of the cells. After 3-AB-treatment, the poly(ADP-ribosyl)ation of nuclear proteins markedly decreases and this results in an increase in both the hypophosphorylated active form of Rb and pRb/E2F complexes. These effects are accompanied by G1 arrest, downregulation of gene products required for proliferation (cyclin D1, beta-catenin, c-Jun, c-Myc and Id2) and upregulation of those implicated in the osteoblastic differentiation (p21/Waf1, osteopontin, osteocalcin, type I collagen, N-cadherins and alkaline phosphatase). Our study suggests that use of PARP inhibitors may induce a remodeling of chromatin with the reprogramming of gene expression and the activation of differentiation.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Benzamides
/
Osteosarcoma
/
Cell Differentiation
/
Enzyme Inhibitors
/
Poly(ADP-ribose) Polymerase Inhibitors
Limits:
Humans
Language:
En
Journal:
FEBS Lett
Year:
2005
Type:
Article
Affiliation country:
Italy