Study of the mechanism of iron chelatingagent-deferoxamine induced cell death in hepatoma HepG2 cells
| Autor: | Guei-Lan Chen, 陳貴蘭 |
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| Rok vydání: | 2000 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 88 Iron is required for cell proliferation and excess iron may be involved in the development of hepatocellular carcinoma. In this study, the effects of deferoxamine (DFO), an iron chelator, in human hepatoma HepG2 cells was investigated. DFO treatment dose dependently reduced the viability and cell growth of HepG2 cells. Moreover, DFO treated cells showed morphological changes including an increase of cell volume as well as intracellular granules. Flow cytometric analyses showed that DFO treatment resulted in an increase of cells in G1-S phase and a decrease of cells in G2-M phase. The levels of p53 and p21 proteins were significantly increased in a time dependent manner after treatment with 25 micro M DFO. The induction of p53 by DFO was abolished by hydrogen peroxide and ferric ammonium citrate. On the other hand, DFO treatment of HepG2 cells resulted in decreased intracellular hydrogen peroxide level with no change in superoxide level. In order to determine the role of hypoxia-inducible factor (HIF)-1α in mediating DFO induced up-regulation of p53, it was found that DFO treatment of HepG2 cells also resulted in increased level of HIF-1α. Moreover, to compare the effects of DFO to mimosine, a well-characterized iron chelator, it was found that both drugs similarly altered cellular levels of p53 and HIF-1α proteins. Using flowcytometry, it was further found that after treatment of HepG2 cells with 25 micro M DFO for 18hr, increased level of transferrin receptors was found on cell surface, indicating that the cells were iron-starved. These results demonstrated that (1) DFO induced accumulation of G1-S cells may involve a p53-dependent pathway (2) The induction of p53 appears to correlate with decreased level of intracellular hydrogen peroxide. (3) DFO treated HepG2 cells showed elevation of HIF-1α and transferrin receptor and the increase of HIF-1α may be involved in regulation of the expression of p53. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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