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GEO help: Mouse over screen elements for information. |
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Status |
Public on Dec 16, 2015 |
Title |
Small molecule-induced bioenergetic reprogramming directs prostate cancer inhibition via UPR signaling |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
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.
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Overall design |
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.
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Contributor(s) |
Rico-Bautista E, Wolf D |
Citation(s) |
23902736 |
Submission date |
Jun 18, 2013 |
Last update date |
Sep 11, 2019 |
Contact name |
Roy M Williams |
E-mail(s) |
rwillia@scripps.edu
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Organization name |
The Scripps Research Institute
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Department |
Regenerative Medicine
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Lab |
Loring
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Street address |
3030 Science Park Road
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City |
La Jolla |
State/province |
CA |
ZIP/Postal code |
92037 |
Country |
USA |
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Platforms (1) |
GPL6883 |
Illumina HumanRef-8 v3.0 expression beadchip |
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Samples (12)
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Relations |
BioProject |
PRJNA208824 |
Supplementary file |
Size |
Download |
File type/resource |
GSE48056_RAW.tar |
3.9 Mb |
(http)(custom) |
TAR |
GSE48056_non_normalized.txt.gz |
1.2 Mb |
(ftp)(http) |
TXT |
Processed data included within Sample table |
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