ArticleMolecular cancer therapeutics2008
Fatty acid synthase inhibition results in a magnetic resonance-detectable drop in phosphocholine.
Article in Molecular cancer therapeutics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 42 citations in OpenAlex.
- FASN promotes lipid metabolism and progression in colorectal cancer via the SP1/PLA2G4B axis.Cell death discovery · 2025Article
- Research Progress towards the Effects of Fatty Acids on the Differentiation and Maturation of Human Induced Pluripotent Stem Cells into Cardiomyocytes.Reviews in cardiovascular medicine · 2023Review
- A cell-based high-throughput screen identifies tyrphostin AG 879 as an inhibitor of animal cell phospholipid and fatty acid biosynthesis.Biochemistry and biophysics reports · 2019Article
- Molecular Effects of Doxorubicin on Choline Metabolism in Breast Cancer.Neoplasia (New York, N.Y.) · 2017Article
- Metabolic positron emission tomography imaging of cancer: Pairing lipid metabolism with glycolysis.World journal of radiology · 2016Article
- Article
- Effect of Pantethine on Ovarian Tumor Progression and Choline Metabolism.Frontiers in oncology · 2016Article
- HR-MAS MRS of the pancreas reveals reduced lipid and elevated lactate and taurine associated with early pancreatic cancer.NMR in biomedicine · 2014Article
- Thyroid hormone responsive protein Spot14 enhances catalysis of fatty acid synthase in lactating mammary epithelium.Journal of lipid research · 2014Article
- Metabolic shifts induced by fatty acid synthase inhibitor orlistat in non-small cell lung carcinoma cells provide novel pharmacodynamic biomarkers for positron emission tomography and magnetic resonance spectroscopy.Molecular imaging and biology · 2013Article
- HDAC inhibition induces increased choline uptake and elevated phosphocholine levels in MCF7 breast cancer cells.PloS one · 2013Article
- Mammalian fatty acid synthase activity from crude tissue lysates tracing ¹³C-labeled substrates using gas chromatography-mass spectrometry.Analytical biochemistry · 2012Article
- Metabolic consequences of treatment with AKT inhibitor perifosine in breast cancer cells.NMR in biomedicine · 2012Article
- Morphoproteomics provides support for TGF-β pathway signaling in the osteoclastogenesis and immune dysregulation of osteolytic Langerhans cell histiocytosis.International journal of clinical and experimental pathology · 2012Article
- Choline metabolism in malignant transformation.Nature reviews. Cancer · 2011Review
- MRS and MRSI guidance in molecular medicine: targeting and monitoring of choline and glucose metabolism in cancer.NMR in biomedicine · 2011Review
- Metabolic effects of signal transduction inhibition in cancer assessed by magnetic resonance spectroscopy.Molecular oncology · 2011Review
- Metabolic tumor imaging using magnetic resonance spectroscopy.Seminars in oncology · 2011Review
- Association of lipid metabolism with ovarian cancer.Current oncology (Toronto, Ont.) · 2010Article
- Biochemistry, molecular biology, and pharmacology of fatty acid synthase, an emerging therapeutic target and diagnosis/prognosis marker.International journal of biochemistry and molecular biology · 2010Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Expression of fatty acid synthase (FASN), the key enzyme in de novo synthesis of long-chain fatty acids, is normally low but increases in cancer. Consequently, FASN is a novel target for cancer therapy. However, because FASN inhibitors can lead to tumor stasis rather than shrinkage, noninvasive methods for assessing FASN inhibition are needed. To this end, we combined (1)H, (31)P, and (13)C magnetic resonance spectroscopy (MRS) (a) to monitor the metabolic consequences of FASN inhibition and (b) to identify MRS-detectable metabolic biomarkers of response. Treatment of PC-3 cells with the FASN inhibitor Orlistat for up to 48 h resulted in inhibition of FASN activity by 70%, correlating with 74% inhibition of fatty acid synthesis. Furthermore, we have determined that FASN inhibition results not only in lower phosphatidylcholine levels but also in a 59% drop in the phospholipid precursor phosphocholine (PCho). This drop resulted from inhibition in PCho synthesis as a result of a reduction in the cellular activity of its synthetic enzyme choline kinase. The drop in PCho levels following FASN inhibition was confirmed in SKOV-3 ovarian cancer cells treated with Orlistat and in MCF-7 breast cancer cells treated with Orlistat as well as cerulenin. Combining data from all treated cells, the drop in PCho significantly correlated with the drop in de novo synthesized fatty acid levels, identifying PCho as a potential noninvasive MRS-detectable biomarker of FASN inhibition in vivo.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.