Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of human A549 lung cancer cells treated with actinomycin D and sapphyrin PCI-2050 a new class of tumor-selective inhibitors of gene expression.

ABSTRACT: The goal of this project was to characterize changes in gene expression in response to the anti-cancer agent sapphyrin PCI-2050. Cultured A549 human lung cancer cells were treated with sapphyrin PCI-2050 or actinomycin D.

ORGANISM(S): Homo sapiens

SUBMITTER: Joseph Gerard Hacia

PROVIDER: E-GEOD-6400 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Synthesis and biologic properties of hydrophilic sapphyrins, a new class of tumor-selective inhibitors of gene expression.

Wang Zhong Z Lecane Philip S PS Thiemann Patricia P Fan Qing Q Cortez Cecilia C Ma Xuan X Tonev Danielle D Miles Dale D Naumovski Louie L Miller Richard A RA Magda Darren D Cho Dong-Gyu DG Sessler Jonathan L JL Pike Brian L BL Yeligar Samantha M SM Karaman Mazen W MW Hacia Joseph G JG

Molecular cancer 20070119

<h4>Background</h4>Sapphyrin analogues and related porphyrin-like species have attracted attention as anticancer agents due to their selective localization in various cancers, including hematologic malignancies, relative to surrounding tissues. Sapphyrins are electron affinic compounds that generate high yields of singlet oxygen formation. Although initially explored in the context of photodynamic therapy, sapphyrins have intrinsic anticancer activity that is independent of their photosensitizin ...[more]

PMID: 17233922

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Project description:Background: Acute respiratory distress syndrome (ARDS) is characterized by refractory hypoxemia caused by accumulation of pulmonary fluid, which is related to inflammatory cell infiltration, impaired tight junction of pulmonary epithelium and impaired Na, K-ATPase function, especially Na, K-ATPase α1 subunit. Up until now, the pathogenic mechanism at the level of protein during lipopolysaccharide- (LPS-) induced ARDS remains unclear. Methods: Using an unbiased, discovery and quantitative proteomic approach, we discovered the differentially expressed proteins binding to Na, K-ATPase α1 between LPS-A549 cells and Control-A549 cells. These Na, K-ATPase α1 interacting proteins were screened by co-immunoprecipitation (Co-IP) technology. Among them, some of the differentially expressed proteins with significant performance were identified and quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The protein interaction network was constructed by the related Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Several differentially expressed proteins were validated by Western blot. Results: Of identified 1598 proteins, 89 were differentially expressed proteins between LPS-A549 cells and Control-A549 cells. Intriguingly, protein-protein interaction network showed that there were 244 significantly enriched co-expression among 60 proteins in the group control-A549. while the group LPS-A549 showed 43 significant enriched interactions among 29 proteins. The related GO and KEGG analysis found evident phenomena of ubiquitination and deubiquitination, as well as the pathways related to autophagy. Among proteins with rich abundance, there were several intriguing ones, including the deubiquitinase (OTUB1), the tight junction protein zonula occludens-1 (ZO-1), the scaffold protein in CUL4B-RING ubiquitin ligase (CRL4B) complexes (CUL4B) and the autophagy-related protein sequestosome-1 (SQSTM1). Conclusions: In conclusion, our proteomic approach revealed targets related to the occurrence and development of ARDS, being the first study to investigate significant differences in Na, K-ATPase α1 interacting proteins between LPS-induced ARDS cell model and control-A549 cell. These proteins may help the clinical diagnosis and facilitate the personalized treatment of ARDS.

Dataset Information

Transcription profiling of human A549 lung cancer cells treated with actinomycin D and sapphyrin PCI-2050 a new class of tumor-selective inhibitors of gene expression.

Publications

Synthesis and biologic properties of hydrophilic sapphyrins, a new class of tumor-selective inhibitors of gene expression.

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