Summary of Study ST003510
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 PR002155. The data can be accessed directly via it's Project DOI: 10.21228/M82J9F 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 | ST003510 |
| Study Title | 3-Hydroxybutyrate Suppresses Colon Cancer Growth through Metabolic Reprogramming and Monocarboxylate Transporter-Mediated Lactate Accumulation - tumor tissue |
| Study Summary | Cancer cachexia (CAC) remains a challenging complication in colon cancer, often leading to poor clinical outcomes. This study investigates the therapeutic potential of 3-hydroxybutyrate (3-HB) in CAC by exploring its effects on tumor growth and cellular metabolism using a colon CAC mouse model and CT26 colon cancer cells. Through NMR-based metabolomics and molecular biology approaches, we reveal that 3-HB slows tumor growth in CAC mice, potentially by increasing lactate accumulation within tumor tissues, modulating key metabolic pathways. Additionally, 3-HB induced oxidative stress and apoptosis in CT26 cells, characterized by elevated reactive oxygen species (ROS) and caspase-3 activation. Mechanistically, 3-HB appears to compete with lactate for monocarboxylate transporters (MCTs), leading to intracellular lactate accumulation, cellular acidification, and tumor suppression. These findings suggest that 3-HB holds promise as a therapeutic agent for colon cancer cachexia, offering new insights into metabolic targeting strategies for cancer treatment. |
| Institute | Xiamen University |
| Last Name | Qiu |
| First Name | Xu |
| Address | Xiamen University |
| qiuxu@stu.xmu.edu.cn | |
| Phone | 13395036603 |
| Submit Date | 2024-09-28 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | fid |
| Analysis Type Detail | NMR |
| Release Date | 2024-10-21 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR002155 |
| Project DOI: | doi: 10.21228/M82J9F |
| Project Title: | NMR spectra of water-soluble extracts of mouse colon cancer tissue and colon cancer CT26 cells |
| Project Type: | NMR |
| Project Summary: | In this study, we investigated the role of 3-Hydroxybutyrate (3-HB) in colon cancer cachexia (CAC). We used a CAC mouse model and murine CT26 colon cancer cells. We used NMR-based metabolomics to investigate 3-HB effects on colon tissue and cell metabolism. |
| Institute: | Xiamen University |
| Department: | Department of Chemical Biology |
| Last Name: | Qiu |
| First Name: | Xu |
| Address: | Xiamen University |
| Email: | qiuxu@stu.xmu.edu.cn |
| Phone: | 13395036603 |
Subject:
| Subject ID: | SU003639 |
| Subject Type: | Mammal |
| Subject Species: | Mus musculus |
| Taxonomy ID: | 10090 |
| Species Group: | Mammals |
Factors:
Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)
| mb_sample_id | local_sample_id | Treatment |
|---|---|---|
| SA386050 | CAC-C3 | CAC |
| SA386051 | CAC-C12 | CAC |
| SA386052 | CAC-C1 | CAC |
| SA386053 | CAC-C16 | CAC |
| SA386054 | CAC-C9 | CAC |
| SA386055 | CAC-C11 | CAC |
| SA386056 | CAC-C17 | CAC |
| SA386057 | CAC-C6 | CAC |
| SA386058 | CACK-CK6 | CACK |
| SA386059 | CACK-CK7 | CACK |
| SA386060 | CACK-CK8 | CACK |
| SA386061 | CACK-CK9 | CACK |
| SA386062 | CACK-CK11 | CACK |
| SA386063 | CACK-CK13 | CACK |
| SA386064 | CACK-CK14 | CACK |
| SA386065 | CACK-CK18 | CACK |
| Showing results 1 to 16 of 16 |
Collection:
| Collection ID: | CO003632 |
| Collection Summary: | Approximately 100 mg of mouse tumor tissue was collected and pre-cooled methanol, chloroform and water (4:4:2.85, v/v) were added in a sequential manner. After vortex mixing, the tissue was completely homogenised using a pre-cooled cryogenic tissue grinder (65 Hz, 3 min). The metabolites were then extracted from the tumor tissue in two phases. The upper aqueous phase was collected by centrifugation at 4°C and 12,000 rpm for 10 min. Nitrogen was used to accelerate volatilisation of methanol from the aqueous phase and transfer to a freeze dryer for removal of water. |
| Sample Type: | Tumors |
Treatment:
| Treatment ID: | TR003648 |
| Treatment Summary: | The tumor-bearing mice were randomly assigned to two groups and subjected to the corresponding interventions. One group of tumor-bearing mice received a daily intraperitoneal injection of ethyl 3-hydroxybutyrate at a dose of 2 mM/kg per day (CACK, n = 8), and correspondingly, the other group of tumor-bearing mice (CAC, n = 8), as well as the control group (NOR, n = 8), was injected daily with an equal volume of PBS. all mice were subjected to a total of 21 days of the intervention. All mice were euthanised on Day 28 post-modelling and sampled. |
Sample Preparation:
| Sampleprep ID: | SP003646 |
| Sampleprep Summary: | The processed metabolite samples were dissolved in NMR buffer (pH 7.4), prepared in D2O, 50 mM PO₄³-, 0.05 mM 3-(trimethylsilyl) propionate sodium-2,2,3,3-d4 (TSP), and subsequently transferred to 5 mm NMR tubes for acquisition of metabolite NMR spectra on a Bruker Avance III HD 850 MHz spectrometer for acquisition of metabolite NMR spectra. One-dimensional (1D) 1H-NMR spectrum acquisition: 1H-NMR spectra were acquired at 298 K on a Bruker Avance III 850 MHz spectrometer (Bruker BioSpin GmbH, Germany) with the pulse sequence NOESYGPPR1D [RD-G1-90°-t-90°-τm-G2-90°-ACQ]. The spectral width was set at 20.00 ppm, with 32 scans, a mixing time of 10 ms, and an additional relaxation delay time of 4 s. |
Analysis:
| Analysis ID: | AN005764 |
| Analysis Type: | NMR |
| Results File: | ST003510_AN005764_Results.txt |
| Units: | ppm |
NMR:
| NMR ID: | NM000293 |
| Analysis ID: | AN005764 |
| Instrument Name: | Bruker Avance III HD 850 MHz |
| Instrument Type: | FT-NMR |
| NMR Experiment Type: | 1D-1H |
| Standard Concentration: | 1 mM TSP |
| Spectrometer Frequency: | 850 MHz |
| NMR Solvent: | H2O+D2O |
| NMR Tube Size: | 5 mm |
| Pulse Sequence: | noesygppr1d [(RD)-90°-t1-90°-τm-90°-ACQ] |
| Receiver Gain: | 57 |
| Offset Frequency: | 15.03 ppm |
| Temperature: | 25 |
| Number Of Scans: | 32 |
| Dummy Scans: | 4 |
| Acquisition Time: | 2 s |
| Spectral Width: | 20 ppm |
| Num Data Points Acquired: | 64 K |
| Line Broadening: | 0.3 Hz |
| Baseline Correction Method: | Auto-baseline correction of integral by abs |
| Chemical Shift Ref Std: | TSP (0.000 ppm) |
