Related Papers
Biomolecules
The roles of sphingosine kinase 1 and 2 in regulating the metabolome and survival of prostate cancer cells
2013 •
Nigel Pyne
We have previously shown that treatment of androgen-sensitive LNCaP cells with the sphingosine kinase (SK) inhibitor SKi (2-(p-hydroxyanilino)-4-(p-chlorophenyl)thiazole) induces the proteasomal degradation of two N-terminal variants of SK1 (SK1a and SK1b), increases C22:0-ceramide and diadenosine 5',5'''-P1,P3-triphosphate (Ap3A) and reduces S1P levels, and promotes apoptosis. We have now investigated the effects of three SK inhibitors (SKi, (S)-FTY720 vinylphosphonate, and (R)-FTY720 methyl ether) on metabolite and sphingolipid levels in androgen-sensitive LNCaP and androgen-independent LNCaP-AI prostate cancer cells. The 51 kDa N-terminal variant of SK1 (SK1b) evades the proteasome in LNCaP-AI cells, and these cells do not exhibit an increase in C22:0-ceramide or Ap3A levels and do not undergo apoptosis in response to SKi. In contrast, the SK inhibitor (S)-FTY720 vinylphosphonate induces degradation of SK1b in LNCaP-AI, but not in LNCaP cells. In LNCaP-AI cells, (...
Journal of Biomolecular Screening
High-Throughput Screening Assay for Sphingosine Kinase Inhibitors in Whole Blood Using RapidFire(R) Mass Spectrometry
2011 •
Matthew Yates, Maureen Highkin
SLAS Discovery
High-Throughput Screening Assay for Sphingosine Kinase Inhibitors in Whole Blood Using RapidFire® Mass Spectrometry
2011 •
Maureen Highkin
To facilitate discovery of compounds modulating sphingosine-1-phosphate (S1P) signaling, the authors used high-throughput mass spectrometry technology to measure S1P formation in human whole blood. Since blood contains endogenous sphingosine (SPH) and S1P, mass spectrometry was chosen to detect the conversion of an exogenously added 17-carbon-long variant of sphingosine, C17SPH, into C17S1P. The authors developed procedures to achieve hom*ogeneous mixing of whole blood in 384-well plates and for a method requiring minimal manipulations to extract S1P from blood in 96- and 384-well plates prior to analyses using the RapidFire® mass spectrometry system.
Molecular Cancer Therapeutics - MOL CANCER THER
Chemosensitizing effects of sphingosine kinase-1 inhibition in prostate cancer cell and animal models
2008 •
Maria Naymark
Cancer Research
Sphingosine Kinase Inhibitors and Cancer: Seeking the Golden Sword of Hercules
Molecular Oncology
NMR metabolomics highlights sphingosine kinase-1 as a new molecular switch in the orchestration of aberrant metabolic phenotype in cancer cells
Paola Turano
Pharmacological Research
Enzymes of sphingosine metabolism as potential pharmacological targets for therapeutic intervention in cancer
2003 •
Olivier Cuvillier
Therapeutic Discovery First Evidence of Sphingosine 1-Phosphate Lyase Protein ExpressionandActivityDownregulation inHumanNeoplasm: Implication for Resistance to Therapeutics in Prostate Cancer
2016 •
Olivier Cuvillier
This is the first report of sphingosine 1-phosphate lyase (SPL) protein expression and enzymatic activity in human neoplasm. This enzyme drives irreversible degradation of sphingosine 1-phosphate (S1P), a bioactive lipid associatedwith resistance to therapeutics in various cancers, including prostate adenocarcinoma. In fresh human prostatectomy specimens, a remarkable decrease in SPL enzymatic activity was found in tumor samples, as compared with normal adjacent tissues. A significant relationship between loss of SPL expression and higher Gleason score was confirmed in tissue microarray (TMA) analysis. Moreover, SPL protein expression and activity were inversely correlated with those of sphingosine kinase-1 (SphK1), the enzyme producing S1P. SPL and SphK1 expressions were independently predictive of aggressive cancer on TMA, supporting the relevance of S1P in prostate cancer. In humanC4-2B andPC-3 cell lines, silencing SPL enhanced survival after irradiation or chemotherapy by decre...
Cancer Research
Sphingosine Kinase-1 as a Chemotherapy Sensor in Prostate Adenocarcinoma Cell and Mouse Models
2005 •
Virginie Garcia
Journal of Cancer Metastasis and Treatment
Mass spectrometry-based metabolomic profiling of prostate cancer -a pilot study
2019 •
Journal of Cancer Metastasis and Treatment
Aim: Prostate cancer (PCa) is the most commonly diagnosed non-skin cancer among men. Serum prostate-specific antigen level is used as a standard PCa biomarker for over 20 years. However, it has only 33% specificity and 86% sensitivity (for the cutoff value for prostate biopsy of > 4 ng/mL). This leads to overdiagnosis and overtreatment. In-depth insight into PCa metabolomics enables discovery of novel PCa biomarkers. Methods: Metabolomic alternation in PCa serum, urine and interstitial fluid was examined using gold-nanoparticle-based laser mass spectrometry imaging. This study included 5 patients who underwent prostate biopsy with positive result, 5 patients with negative result and 10 healthy controls. Results: Over two hundred differentiating metabolites (87 in urine, 54 in serum and 78 in interstitial fluid) were detected. Four, twenty two and ten metabolites from urine, serum and interstitial fluid respectively showed statistical significant differential abundance between cancer and control group. Conclusion: Comprehensive metabolomic profile of PCa has been identified. Out of 36 metabolites, 20 were identified and should be further evaluated in clinical trials as a potential PCa biomarker. Urine concentration of triglyceride (12:0/20:1) showed over 10 times higher abundance in PCa samples in comparison to healthy controls and is considered the most promising potential biomarker.
