Summary of Study ST002856
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001788. The data can be accessed directly via it's Project DOI: 10.21228/M8KX5C This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST002856 |
| Study Title | Validation of on-target effect of IACS-010759 in vehicle- and Enzalutamide-treated 16D cells |
| Study Summary | In this study, we sought to validate that 30nM IACS-010759, a complex I inhibitor, had an on-target effect in vehicle- and Enzalutamide-treated 16D prostate cancer cells. |
| Institute | University of California, Los Angeles |
| Laboratory | Goldstein Lab |
| Last Name | Giafaglione |
| First Name | Jenna |
| Address | 610 Charles E Young Dr S, Los Angeles, CA, 90024, USA |
| jgiafaglione@g.ucla.edu | |
| Phone | 408-728-3065 |
| Submit Date | 2023-09-11 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | d |
| Analysis Type Detail | GC-MS |
| Release Date | 2023-09-13 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR001788 |
| Project DOI: | doi: 10.21228/M8KX5C |
| Project Title: | MYC is a regulator of AR inhibition-induced metabolic requirements in prostate cancer |
| Project Summary: | Advanced prostate cancers are treated with therapies targeting the androgen receptor (AR) signaling pathway. While many tumors initially respond to AR inhibition, nearly all develop resistance. It is critical to understand how prostate tumor cells respond to AR inhibition in order to exploit therapy-induced phenotypes prior to the outgrowth of treatment-resistant disease. Here, we comprehensively characterize the effect of AR blockade on prostate cancer metabolism using transcriptomics, metabolomics and bioenergetics approaches. The metabolic response to AR inhibition is defined by reduced glycolysis, robust elongation of mitochondria, and increased reliance on mitochondrial oxidative metabolism. We establish DRP1 activity and MYC signaling as mediators of AR blockade-induced metabolic phenotypes. Rescuing DRP1 phosphorylation after AR inhibition restores mitochondrial fission, while rescuing MYC restores glycolytic activity and prevents sensitivity to complex I inhibition. Our study provides new insight into the regulation of treatment-induced metabolic phenotypes and vulnerabilities in prostate cancer. |
| Institute: | UCLA |
| Laboratory: | Goldstein Lab |
| Last Name: | Giafaglione |
| First Name: | Jenna |
| Address: | 610 Charles E Young Dr S, Los Angeles, CA, 90024, USA |
| Email: | jgiafaglione@g.ucla.edu |
| Phone: | 408-728-3065 |
Subject:
| Subject ID: | SU002968 |
| Subject Type: | Cultured cells |
| Subject Species: | Homo sapiens |
| Taxonomy ID: | 9606 |
Factors:
Subject type: Cultured cells; Subject species: Homo sapiens (Factor headings shown in green)
| mb_sample_id | local_sample_id | Treatment |
|---|---|---|
| SA308790 | LT Enza-IACS-2 | 30nM IACS-010759 |
| SA308791 | LT Enza-IACS-1 | 30nM IACS-010759 |
| SA308792 | Naive-IACS-3 | 30nM IACS-010759 |
| SA308793 | Naive-IACS-1 | 30nM IACS-010759 |
| SA308794 | Naive-IACS-2 | 30nM IACS-010759 |
| SA308795 | LT Enza-IACS-3 | 30nM IACS-010759 |
| SA308796 | LT Enza-NT3 | Vehicle (DMSO) |
| SA308797 | LT Enza-NT1 | Vehicle (DMSO) |
| SA308798 | Naive-NT2 | Vehicle (DMSO) |
| SA308799 | Naive-NT3 | Vehicle (DMSO) |
| SA308800 | Naive-NT1 | Vehicle (DMSO) |
| SA308801 | LT Enza-NT2 | Vehicle (DMSO) |
| Showing results 1 to 12 of 12 |
Collection:
| Collection ID: | CO002961 |
| Collection Summary: | Vehicle- and Enzalutamide-treated 16D cells were cultured with 30nM IACS-010759 for 24 hours |
| Sample Type: | Cultured cells |
Treatment:
| Treatment ID: | TR002977 |
| Treatment Summary: | Vehicle- and Enzalutamide-treated 16D cells were cultured with 30nM IACS-010759 in U13C-glucose-containing media for 24 hours |
Sample Preparation:
| Sampleprep ID: | SP002974 |
| Sampleprep Summary: | Cell plates were placed on ice and quickly washed with ice-cold 0.9% (w/v) NaCl. Cells were immediately treated with 500 μL of ice-cold MeOH and 200 μL water containing 1 μg of the internal standard norvaline. Cells were then scraped and placed in 1.5 mL centrifuge tubes kept on ice. Next, 500 μL of chloroform was added, after which samples were vortexed for 1 minute and then spun at 10,000g for 5 minutes at 4C. The aqueous layer was transferred to a GC/MS sample vial and dried overnight using a refrigerated CentriVap. |
Combined analysis:
| Analysis ID | AN004678 |
|---|---|
| Analysis type | MS |
| Chromatography type | GC |
| Chromatography system | Agilent 7890A |
| Column | Agilent DB5-MS (30m x 0.25mm, 0.25um) |
| MS Type | EI |
| MS instrument type | GC-TOF |
| MS instrument name | Agilent 5977B |
| Ion Mode | POSITIVE |
| Units | abundance |
Chromatography:
| Chromatography ID: | CH003520 |
| Instrument Name: | Agilent 7890A |
| Column Name: | Agilent DB5-MS (30m x 0.25mm, 0.25um) |
| Column Temperature: | 23 |
| Flow Gradient: | N/A (GC-MS) |
| Flow Rate: | 1 ml/min |
| Solvent A: | N/A (GC-MS) |
| Solvent B: | N/A (GC-MS) |
| Chromatography Type: | GC |
MS:
| MS ID: | MS004425 |
| Analysis ID: | AN004678 |
| Instrument Name: | Agilent 5977B |
| Instrument Type: | GC-TOF |
| MS Type: | EI |
| MS Comments: | Data was analyzed using Agilent MassHunter software. Stable isotope tracing data was corrected for natural abundance of heavy isotopes with FluxFix software using a reference set of unlabeled metabolite standards2. |
| Ion Mode: | POSITIVE |
