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Induction of apoptosis in p53-deficient human hepatoma cell line by wild-type p53 gene transduction: inhibition by antioxidant.
- Source :
-
Molecules and cells [Mol Cells] 2001 Aug 31; Vol. 12 (1), pp. 17-24. - Publication Year :
- 2001
-
Abstract
- We investigated the role of wild-type (wt)-p53 as an inducer of apoptotic cell death in human hepatoma cell lines. Following the retrovirus-mediated transduction of the wt-p53 gene, Hep3B cells lacking the endogenous p53 expression began to die through apoptosis in 4 h. They showed a maximal apoptotic death at 12 h, whereas HepG2 cells expressing endogenous p53 did not. However, the transduction of the wt-p53 gene elicited growth suppression of both Hep3B and HepG2 cells. P21(WAF1/CIP1), a p53-inducible cell cycle inhibitor, was induced, not only in Hep3B cells undergoing apoptosis, but also in HepG2 cells. The kinetics of the p21(WAF1/CIP1) induction, DNA fragmentation, and growth suppression of the Hep3B cells showed that DNA fragmentation and growth suppression progressed rapidly following p21(WAF1/CIP1) accumulation. N-acetyl-cysteine or glutathione, potent antioxidants, strongly inhibited the DNA fragmentation, but did not reduce the elevated level of p21(WAF1/CIP1). These findings suggested that p21(WAF1/CIP1) was not a critical mediator for the execution of p53-mediated apoptosis, although it contributed to the growth inhibition of cells undergoing apoptosis. Furthermore, p53-mediated apoptosis could be repressed by antioxidants.
- Subjects :
- Acetylcysteine pharmacology
Carcinoma, Hepatocellular
Cell Survival
Cyclin-Dependent Kinase Inhibitor p21
Cyclin-Dependent Kinases metabolism
Cyclins genetics
DNA Fragmentation
Free Radical Scavengers pharmacology
Glutathione pharmacology
Humans
In Situ Nick-End Labeling
Liver Neoplasms
Retroviridae genetics
Retroviridae metabolism
Tumor Cells, Cultured
Antioxidants pharmacology
Apoptosis drug effects
Cyclins metabolism
Genes, p53
Transduction, Genetic
Tumor Suppressor Protein p53 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1016-8478
- Volume :
- 12
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Molecules and cells
- Publication Type :
- Academic Journal
- Accession number :
- 11561726