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| Status |
Public on May 05, 2011 |
| Title |
Expression data comparing azacitidine and decitabine in non-small cell lung cancer lines |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Azacitidine (AZA) and decitabine (DAC) are cytidine azanucleoside analogs with clinical activity in myelodysplastic syndromes (MDS) and potential activity in solid tumors. To better understand the mechanism of action of these drugs, we examined the effects of AZA and DAC in a panel of non-small cell lung cancer (NSCLC) cell lines. Of 5 NSCLC lines tested in a cell viability assay, all were sensitive to AZA (EC50 of 1.8–10.5 µM), while only H1299 cells were equally sensitive to DAC (EC50 of 5.1 µM). In the relatively DAC-insensitive cell line A549, both AZA and DAC caused DNA methyltransferase I depletion and DNA hypomethylation; however, only AZA significantly induced markers of DNA damage and apoptosis, suggesting that mechanisms in addition to, or other than, DNA hypomethylation are important for AZA-induced cell death. Cell cycle analysis indicated that AZA induced an accumulation of cells in sub-G1 phase, whereas DAC mainly caused an increase of cells in G2/M. Gene expression analysis of AZA- and DAC-treated cells revealed strikingly different profiles, with many genes distinctly regulated by each drug. In summary, while both AZA and DAC caused DNA hypomethylation, distinct effects were demonstrated on regulation of gene expression, cell cycle, DNA damage, and apoptosis.
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| Overall design |
A549 and H1299 cells were treated with a dose range (0.3–3.0 μM) of AZA or DAC for 48 hours, and effects on gene expression were assessed by microarray analysis.
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| Contributor(s) |
Nguyen AN, Richard N, Brady H |
| Citation |
Azacitidine and decitabine have different mechanisms of action in non-small cell lung cancer cell lines. Authors: Aaron N Nguyen, Paul W Hollenbach, Normand Richard, et al. Published Date September 2010 , Volume 2010:1(Default) Pages 119 - 140 DOI 10.2147/LCTT.S11726
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| Submission date |
May 05, 2011 |
| Last update date |
Dec 06, 2018 |
| Contact name |
Helen Brady |
| E-mail(s) |
hbrady@celgene.com
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| Organization name |
Celgene
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| Street address |
4550 Towne Centre Ct
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| City |
San Diego |
| State/province |
CA |
| ZIP/Postal code |
92128 |
| Country |
USA |
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| Platforms (1) |
| GPL571 |
[HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array |
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| Samples (28)
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| Relations |
| BioProject |
PRJNA140293 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE29077_RAW.tar |
62.4 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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