Summary of Study ST002967
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 PR001846. The data can be accessed directly via it's Project DOI: 10.21228/M83H81 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 | ST002967 |
| Study Title | Lipidomics study of FASN inhibition in HT-29 and HCT 116 spheroids |
| Study Summary | Cancerous cells synthesize most of their lipids de novo to keep up with their rapid growth and proliferation. Fatty acid synthase (FAS) is a key enzyme in the lipogenesis pathway that is upregulated in many cancers and has gained popularity as a druggable target of interest for cancer treatment. The first FAS inhibitor discovered, cerulenin, initially showed promise for chemotherapeutic purposes until it was observed that it had adverse side effects in mice. TVB2640 (Denifanstat), is part of the newer generation of inhibitors. With multiple generations of FAS inhibitors being developed, it is vital to understand their distinct molecular downstream effects to elucidate potential interactions in the clinic. Here, we profile the lipidome of two different colorectal cancer (CRC) spheroids treated with a generation 1 inhibitor (cerulenin) or a generation 2 inhibitor (TVB-2640). We observe that the cerulenin causes drastic changes to the spheroid morphology as well as alterations to the lipid droplets found within CRC spheroids. TVB-2640 causes higher abundances of polyunsaturated fatty acids (PUFAs) whereas cerulenin causes decreased abundance of PUFAs. The increase in PUFAs in TVB-2640 exposed spheroids indicates it is causing cells to die via a ferroptotic mechanism rather than a conventional apoptotic or necrotic mechanism. |
| Institute | The Ohio State University |
| Department | Chemistry and Biochemistry |
| Laboratory | Amanda Hummon Lab |
| Last Name | Fries |
| First Name | Brian |
| Address | 460 W 12th Ave, Columbus, OH 43210 |
| fries.94@osu.edu | |
| Phone | 9375221195 |
| Submit Date | 2023-11-08 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | d |
| Analysis Type Detail | LC-MS |
| Release Date | 2024-04-02 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
| Analysis ID | AN004875 |
|---|---|
| Analysis type | MS |
| Chromatography type | Reversed phase |
| Chromatography system | 1290 Infinity II UHPLC (Agilent) |
| Column | Waters ACQUITY UPLC BEH C18 (100 x 2.1mm, 1.7um) |
| MS Type | ESI |
| MS instrument type | QTOF |
| MS instrument name | Agilent 6545 QTOF |
| Ion Mode | UNSPECIFIED |
| Units | pmol/ug of Protein |
Chromatography:
| Chromatography ID: | CH003678 |
| Chromatography Summary: | Dried lipid extracts were resuspended in 9:1 in methanol/toluene to obtain a protein equivalent concentration of 2 µg/µL. At the same time, a pooled sample was created by taking an equal volume from each sample in the study. Diluted samples were injected on a 1290 Infinity II UHPLC System (Agilent Technologies Inc., Santa Clara, California, USA) onto an ACQUITY PREMIER BEH C18 column (1.7 μm, 2.1 x 100 mm, Waters Corporation, Belford, MA, USA) for reversedphase chromatography which was maintained at 50 °C with a constant flow rate at 0.400 ml/min, using a gradient of mobile phase A (50:50 acetonitrile/H2O with 5 mM ammonium formate) and mobile phase B (90:10 isopropanol/acetonitrile with 5 mM ammonium formate). The gradient program was as follows: 0 – 5 min, 15 – 40 %B; 5 – 6 min, 40 – 50 %B; 6 – 30 min, 50 – 95 %B; 30 – 32 min, hold 95 %B. A 10-minute post time was enabled which held the solvent composition at 15 %B before analyzing the next sample. |
| Instrument Name: | 1290 Infinity II UHPLC (Agilent) |
| Column Name: | Waters ACQUITY UPLC BEH C18 (100 x 2.1mm, 1.7um) |
| Column Temperature: | 50 |
| Flow Gradient: | : 0 – 5 min, 15 – 40 %B; 5 – 6 min, 40 – 50 %B; 6 – 30 min, 50 – 95 %B; 30 – 32 min, hold 95 %B. A 10-minute post time was enabled which held the solvent composition at 15 %B before analyzing the next sample |
| Flow Rate: | 0.400 mL/min |
| Solvent A: | 50:50 ACN:H20 with 5 mM ammonium formate |
| Solvent B: | 90:10 IPA/ACN with 5 mM ammonium formate |
| Chromatography Type: | Reversed phase |
