| Methoxyamine sensitizes the resistant glioblastoma T98G cell line to the alkylating agent temozolomide. | |
| | |
MedLine Citation:
|
PMID: 22828727 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Chemoresistance represents a major obstacle to successful treatment for malignant glioma with temozolomide. N (7)-methyl-G and N (3)-methyl-A adducts comprise more than 80 % of DNA lesions induced by temozolomide and are processed by the base excision repair, suggesting that the cellular resistance could be caused, in part, by this efficient repair pathway, although few studies have focused on this subject. The aim of this study was to evaluate the cellular responses to temozolomide treatment associated with methoxyamine (blocker of base excision repair) in glioblastoma cell lines, in order to test the hypothesis that the blockage of base excision repair pathway might sensitize glioblastoma cells to temozolomide. For all the tested cell lines, only T98G showed significant differences between temozolomide and temozolomide plus methoxyamine treatment, observed by reduced survival rates, enhanced the levels of DNA damage, and induced an arrest at G2-phase. In addition, ~10 % of apoptotic cells (sub-G1 fraction) were observed at 48 h. Western blot analysis demonstrated that APE1 and FEN1 presented a slightly reduced expression levels under the combined treatment, probably due to AP sites blockade by methoxyamine, thus causing a minor requirement of base excision repair pathway downstream to the AP removal by APE1. On the other hand, PCNA expression in temozolomide plus methoxyamine-treated cells does not rule out the possibility that such alteration might be related to the blockage of cell cycle (G2-phase), as observed at 24 h of recovery time. The results obtained in the present study demonstrated the efficiency of methoxyamine to overcome glioblastoma resistance to temozolomide treatment. |
| | |
Authors:
|
Ana P Montaldi; Elza T Sakamoto-Hojo |
Related Documents
:
|
6579547 - Involvement of a cell-surface glycoprotein in the cell-sorting process of dictyostelium... 18621387 - Cellular clot formation in a sipunculan worm: entrapment of foreign particles, cell dea... 16923127 - Dynamics of yeast prion aggregates in single living cells. 3039657 - Cell-autonomous determination of cell-type choice in dictyostelium development by cell-... 18473587 - Evidence for the presence of complex carbohydrates in candida albicans cell wall glycop... 16019927 - Spontaneous and gamma-ray-induced sister chromatid exchanges in patients with carcinoma... |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2012-7-25 |
Journal Detail:
|
Title: Clinical and experimental medicine Volume: - ISSN: 1591-9528 ISO Abbreviation: - Publication Date: 2012 Jul |
Date Detail:
|
Created Date: 2012-7-25 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 100973405 Medline TA: Clin Exp Med Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
Department of Genetics, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Effects of a Complete Smoking Ban on Inpatients at an Intermediate to Long-Term Psychiatric Facility...
Next Document: A cardiac tissue-specific binding agent of troponin I.