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.

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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
Email	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

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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

Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id	local_sample_id	Sample source	Treatment
SA386050	CAC-C3	colon tumor tissue	CAC
SA386051	CAC-C12	colon tumor tissue	CAC
SA386052	CAC-C1	colon tumor tissue	CAC
SA386053	CAC-C16	colon tumor tissue	CAC
SA386054	CAC-C9	colon tumor tissue	CAC
SA386055	CAC-C11	colon tumor tissue	CAC
SA386056	CAC-C17	colon tumor tissue	CAC
SA386057	CAC-C6	colon tumor tissue	CAC
SA386058	CACK-CK6	colon tumor tissue	CACK
SA386059	CACK-CK7	colon tumor tissue	CACK
SA386060	CACK-CK8	colon tumor tissue	CACK
SA386061	CACK-CK9	colon tumor tissue	CACK
SA386062	CACK-CK11	colon tumor tissue	CACK
SA386063	CACK-CK13	colon tumor tissue	CACK
SA386064	CACK-CK14	colon tumor tissue	CACK
SA386065	CACK-CK18	colon tumor tissue	CACK

Showing results 1 to 16 of 16

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.

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.

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)