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| Status |
Public on Dec 22, 2010 |
| Title |
H3K9K14ac ChIP-chip in lung cancer cells treated with histone deacetylase inhibitor |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by genome tiling array
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| Summary |
Lung cancer is the leading cause of cancer mortality worldwide, yet the therapeutic strategy for advanced non-small cell lung cancer (NSCLC) is limitedly effective. In addition, validated histone deacetylase (HDAC) inhibitors for the treatment of solid tumors remain to be developed. Here, we propose a novel HDAC inhibitor, OSU-HDAC-44, as a chemotherapeutic drug for NSCLC. OSU-HDAC-44 was a pan-HDAC inhibitor and exhibits 3-4 times more effectiveness than suberoylanilide hydroxamic acid (SAHA) in suppressing cell viability in various NSCLC cell lines. Upon OSU-HDAC-44 treatment, mitosis and cytokinesis were inhibited and subsequently led to mitochondria-mediated apoptosis. The cytokinesis inhibition resulted from OSU-HDAC-44-mediated degradation of mitosis and cytokinesis regulators Auroroa B and survivin. The deregulation of F-actin dynamics induced by OSU-HDAC-44 was associated with reduction in RhoA activity resulting from srGAP1 induction. Chromatin-immunoprecipitation-on-chip analysis revealed that OSU-HDAC-44 induced chromatin loosening and facilitated transcription of genes involved in crucial signaling pathways such as apoptosis, axon guidance and protein ubiquitination. Finally, OSU-HDAC-44 efficiently inhibited A549 xenograft tumor growth and induced acetylation of histone and non-histone proteins and apoptosis in vivo. Collectively, our data provide compelling evidence that OSU-HDAC-44 is a potent HDAC targeted inhibitor and can be tested for NSCLC chemotherapy.
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| Overall design |
ChIP-chip analysis for H3K9K14ac in A549, H1299 and CL1-1 lung cancer cells treated with 2.5 uM histone deacetylase inhibitor, OSU-HDAC-44, for 2 hours.
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| Contributor(s) |
Tang Y, Wen W, Chang J, Wei T, Tan YC, Chen C, Chen C, Wang Y |
| Citation(s) |
20856855 |
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| Submission date |
Feb 12, 2010 |
| Last update date |
Mar 22, 2012 |
| Contact name |
Yi-Ching Wang |
| E-mail(s) |
ycw5798@mail.ncku.edu.tw
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| Phone |
+886-6-2353535
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| Organization name |
National Cheng Kung University
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| Department |
Department of Pharmacology, College of Medicine
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| Street address |
No.1, University Road, Tainan 70101, Taiwan, R. O. C.
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| City |
Tainan |
| ZIP/Postal code |
70101 |
| Country |
Taiwan |
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| Platforms (1) |
| GPL7408 |
Nimblegen HG18 RefSeq promoter array |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA125343 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE20304_RAW.tar |
132.7 Mb |
(http)(custom) |
TAR (of PAIR, TXT) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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