Abstract
Background: Overexpression of the transcription factor E2F-1 provokes apoptosis in cancer cells; the mechanism, however, is not completely understood. We sought to evaluate E2F-1 gene therapy in human colon cancer and to investigate the apoptotic pathway involved. Methods: Adenoviral vectors were used to transfect the E2F-1 gene (Ad5E2F-1) or the control gene luciferase (Ad5Luc) into four human colon carcinoma cell lines. Apoptosis was confirmed by flow cytometry and poly (ADP-ribose) polymerase cleavage. Expression of apoptotic factors was determined with Western blot analysis. Inhibitory assays were used to determine the involvement of caspases in the apoptotic pathway. Results: Overexpression of E2F-1 was evident in all cells treated with Ad5E2F-1; upregulation of Bcl-2, and activation of caspases were noted. The apoptosis-inducing factor in the cytosolic fraction was markedly upregulated after Ad5E2F-1 treatment. E2F-1 overexpression inhibited proliferation and induced significant apoptosis in all cell lines (P < .005). This apoptotic response could be only partially blocked by caspase inhibitors. Conclusions: These findings demonstrate that E2F-1 induces apoptosis and inhibits proliferation in human colon cancer cell lines. The marked upregulation of apoptosis-inducing factor and the fact that E2F-1-induced apoptosis is incompletely blocked by caspase inhibitors suggest a caspase-independent pathway of E2F-1-mediated apoptosis, reported here for the first time.
Original language | English (US) |
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Pages (from-to) | 314-322 |
Number of pages | 9 |
Journal | Annals of surgical oncology |
Volume | 10 |
Issue number | 3 |
DOIs | |
State | Published - 2003 |
Keywords
- Apoptosis
- Apoptosis-inducing factor
- Colon cancer
- E2F-1
- Mitochondrion
ASJC Scopus subject areas
- Surgery
- Oncology