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Title: Small molecule-induced bioenergetic reprogramming directs prostate cancer inhibition via UPR signaling      
dateReleased:
12-16-2015
description:
We previously identified SMIP004 (N-(4-butyl-2-methyl-phenyl) acetamide), as a novel inducer of cancer-cell selective apoptosis of human prostate cancer cells. SMIP004 decreased the levels of positive cell cycle regulators, such as cyclin A, CDK4 and SKP2 while upregulating cyclin-dependent kinase inhibitors p27 and p21, resulting in G1 arrest and inhibition of colony formation in soft agar. However, the mechanism of SMIP004-induced cancer cell selective apoptosis remained unknown. We used profiling to unravel a SMIP004-induced pro-apoptotic pathway, which initiates with bioenergetic reprogramming at the level of mitochondria. SMIP004 causes downregulation of aerobic glycolysis, rapid upregulation of components of the mitochondrial electron transport chain, and oxidative stress. The latter, in turn, elicits cell cycle arrest by rapidly targeting cyclin D1 for proteasomal degradation, drives transcriptional downregulation of the androgen receptor, and activates pro-apoptotic signaling through the unfolded protein response and MAPK activation. Finally SMIP004 was found to potently inhibit the growth of prostate and breast cancer xenografts in mice. There are two biological replicates SMIP004Rep1 and SMIP004Rep2 and two technical replicates for each biological replicates (SMIP004 Rep1_1 and SMIP004 Rep1_2). Total RNA from cells treated with 40 uM SMIP004 for 24 h, vehicle or positive controls (Roscovitine, 20uM, Campthotecin 500 nMM, Bortezomib 50 nM) was obtained using the RNeasy Mini Kit. The drug treated and control samples were compared.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-48056
refinement:
raw
alternateIdentifiers:
48056
keywords:
functional genomics
dateModified:
12-19-2015
availability:
available
types:
gene expression
name:
Homo sapiens
ID:
A-MEXP-1172
name:
Illumina HumanRef-8 v3.0 Expression BeadChip
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-48056/E-GEOD-48056.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-48056/E-GEOD-48056.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE48056
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress

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