Superoxide dismutase 1 (SOD1) is a target for a small molecule identified in a screen for inhibitors of the growth of lung adenocarcinoma cell lines Journal Article

   

Authors:	Somwar, R.; Erdjument-Bromage, H.; Larsson, E.; Shum, D.; Lockwood, W. W.; Yang, G.; Sander, C.; Ouerfelli, O.; Tempst, P. J.; Djaballah, H.; Varmus, H. E.
Article Title:	Superoxide dismutase 1 (SOD1) is a target for a small molecule identified in a screen for inhibitors of the growth of lung adenocarcinoma cell lines
Abstract:	We previously described four small molecules that reduced the growth of lung adenocarcinoma cell lines with either epidermal growth factor receptor (EGFR) or KRAS mutations in a high-throughout chemical screen. By combining affinity proteomics and gene expression analysis, we now propose superoxide dismutase 1 (SOD1) as the most likely target of one of these small molecules, referred to as lung cancer screen 1 (LCS-1). siRNAs against SOD1 slowed the growth of LCS-1 sensitive cell lines; conversely, expression of a SOD1 cDNA increased proliferation of H358 cells and reduced sensitivity of these cells to LCS-1. In addition, SOD1 enzymatic activity was inhibited in vitro by LCS-1 and two closely related analogs. These results suggest that SOD1 is an LCS-1-binding protein that may act in concert with mutant proteins, such as EGFR and KRAS, to promote cell growth, providing a therapeutic target for compounds like LCS-1.
Keywords:	unclassified drug; human cell; cancer growth; adenocarcinoma; cell proliferation; cell division; apoptosis; gene expression profiling; etoposide; lung neoplasms; epidermal growth factor receptor; small interfering rna; rna, small interfering; cancer cell culture; in vitro study; enzyme activity; cell line, tumor; cancer inhibition; lung adenocarcinoma; drug binding site; k ras protein; superoxide dismutase; complementary dna; molecularly targeted therapy; affinity chromatography; chemical biology; gene interaction network; target discovery and validation; 4,5 dichloro 2 meta tolylpyridazin 3(2h)one
Journal Title:	Proceedings of the National Academy of Sciences of the United States of America
Volume:	108
Issue:	39
ISSN:	0027-8424
Publisher:	National Academy of Sciences
Date Published:	2011-09-27
Start Page:	16375
End Page:	16380
Language:	English
DOI:	10.1073/pnas.1113554108
PROVIDER:	scopus
PMCID:	PMC3182729
PUBMED:	21930909
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-80053628065&partnerID=40&md5=9fae8ca203c147a4c9fc01c15a9686f0
Notes:	--- - "Export Date: 2 November 2011" - "CODEN: PNASA" - "Source: Scopus"

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