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E2F1 enhances 8-chloro-adenosine-induced G2/M arrest and apoptosis in A549 and H1299 lung cancer cells.
- Source :
-
Biochemistry. Biokhimiia [Biochemistry (Mosc)] 2012 Mar; Vol. 77 (3), pp. 261-9. - Publication Year :
- 2012
-
Abstract
- The E2F1 transcription factor is a well known regulator of cell proliferation and apoptosis, but its role in response to DNA damage is less clear. 8-Chloro-adenosine (8-Cl-Ado), a nucleoside analog, can inhibit proliferation in a variety of human tumor cells. However, it is still elusive how the agent acts on tumors. Here we show that A549 and H1299 cells formed DNA double-strand breaks after 8-Cl-Ado exposure, accompanied by E2F1 upregulation at protein level. Overexpressed wild-type (E2F1-wt) colocalized with double-strand break marker γ-H2AX and promoted G2/M arrest in 8-Cl-Ado-exposed A549 and H1299, while expressed S31A mutant of E2F1 (E2F1-mu) significantly reduced ability to accumulate at sites of DNA damage and G2/M arrest, suggesting that E2F1 is required for activating G2/M checkpoint pathway upon DNA damage. Transfection of either E2F1-wt or E2F1-mu plasmid promoted apoptosis in 8-Cl-Ado-exposed cells, indicating that 8-Cl-Ado may induce apoptosis in E2F1-dependent and E2F1-independent ways. These findings demonstrate that E2F1 plays a crucial role in 8-Cl-Ado-induced G2/M arrest but is dispensable for 8-Cl-Ado-induced apoptosis. These data also suggest that the mechanism of 8-Cl-Ado action is complicated.
- Subjects :
- 2-Chloroadenosine pharmacology
Adenocarcinoma drug therapy
Adenocarcinoma genetics
Adenocarcinoma metabolism
Adenocarcinoma of Lung
Cell Line, Tumor
Cell Proliferation drug effects
DNA Damage drug effects
E2F1 Transcription Factor genetics
Humans
Lung Neoplasms drug therapy
Lung Neoplasms genetics
Lung Neoplasms metabolism
2-Chloroadenosine analogs & derivatives
Adenocarcinoma physiopathology
Antineoplastic Agents pharmacology
Apoptosis drug effects
E2F1 Transcription Factor metabolism
G2 Phase Cell Cycle Checkpoints drug effects
Lung Neoplasms physiopathology
M Phase Cell Cycle Checkpoints drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1608-3040
- Volume :
- 77
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Biochemistry. Biokhimiia
- Publication Type :
- Academic Journal
- Accession number :
- 22803943
- Full Text :
- https://doi.org/10.1134/S0006297912030042