E2F1-mediated DNA damage is implicated in 8-Cl-adenosine-induced chromosome missegregation and apoptosis in human lung cancer H1299 cells

Although E2F1-mediated DNA double-stranded breaks (DSBs) and tetraploid have been extensively studied, the role of E2F1 in mitotic catastrophe is still unknown. We have previously shown that 8-chloro-adenosine (8-Cl-Ado) induces DNA DSBs and aberrant mitosis in human lung cancer cells, followed by d...

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Bibliographic Details
Published in:Molecular and cellular biochemistry 2013-12, Vol.384 (1-2), p.187-196
Main Authors: Han, Yu-Ying, Zhou, Zhe, Cao, Ji-Xiang, Jin, Ya-Qiong, Li, Shu-Yan, Ni, Ju-Hua, An, Guo-Shun, Zhang, Yu-Xiang, Jia, Hong-Ti
Format: Article
Language:English
Subjects:
2-Chloroadenosine - analogs & derivatives
2-Chloroadenosine - pharmacology
Apoptosis
Apoptosis - drug effects
Apoptosis - genetics
Biochemistry
Biomedical and Life Sciences
Cardiology
Cell Cycle - genetics
Cell Line, Tumor
Cell Proliferation
Chromosome Aberrations
Chromosome Segregation - drug effects
Chromosome Segregation - genetics
Chromosomes
Chromosomes - genetics
DNA Breaks, Double-Stranded
DNA damage
Down-Regulation
E2F1 Transcription Factor - metabolism
Histones - metabolism
Humans
Life Sciences
Lung cancer
Lung Neoplasms - genetics
Lung Neoplasms - pathology
Medical Biochemistry
Mitosis - drug effects
Mitosis - genetics
Oncology
RNA Interference
RNA, Small Interfering
Tetraploidy
Tumor Suppressor Protein p14ARF - metabolism
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Summary:Although E2F1-mediated DNA double-stranded breaks (DSBs) and tetraploid have been extensively studied, the role of E2F1 in mitotic catastrophe is still unknown. We have previously shown that 8-chloro-adenosine (8-Cl-Ado) induces DNA DSBs and aberrant mitosis in human lung cancer cells, followed by delayed apoptosis. Here, we demonstrate that E2F1-mediated DNA damage is implicated in 8-Cl-Ado-induced chromosome missegregation and apoptosis in lung cancer H1299 cells. We showed that E2F1 was accumulated upon 8-Cl-Ado-induced DNA DSBs. Induction of E2F1 by 8-Cl-Ado caused DNA damage in cycling cells including M cells. In contrast, silencing of E2F1 expression decreased 8-Cl-Ado-induced DNA DSBs, particularly eliminated E2F1-mediated mitotic DNA damage. Over-expression of E2F1 and/or 8-Cl-Ado exposure resulted in aberrant mitotic spindles and chromosome segregation errors. Furthermore, over-expression of E2F1 expression enhanced 8-Cl-Ado-induced apoptosis. Together, our data indicate that E2F1-mediated DNA damage, in particular mitotic DNA damage, is an important fraction of 8-Cl-Ado-induced DNA damage, which is implicated in 8-Cl-Ado-induced mitotic catastrophe and delayed apoptosis. Induction of E2F1 by 8-Cl-Ado may contribute at least partly to the drug-inhibited proliferation of cancer cells.
ISSN:0300-8177
1573-4919
DOI:10.1007/s11010-013-1797-1