Hesperidin had modulatory effects on UC pathogenesis, which might be through alleviating colonic sphingosine phosphate phosphatase 2 messenger RNA expression and sphingosine kinase-1 levels, thus suppressing the subsequent downstream inflammatory and apoptotic cascades represented by decreased macrophage inflammatory protein-1α and enhancement of B-cell lymphoma 2 immunohistochemistry expression.
Similarly, downregulation of SphKs by siRNA inhibited glioma cell proliferation, and the cell cycle was arrested in G(2) /M phase when SphK1 was inhibited.
Collectively, our results indicate that regulation of the Akt/FOXO3a/Bim pathway may be a novel mechanism by which SPHK1 protects glioma cells from apoptosis, thereby involved in glioma tumorigenesis.
We found that SK1 overexpression in HEK cells or its down-regulation in glioma or breast cancer cells modulated extracellular S1P levels accordingly, which in turn increased or decreased both migration and tube formation in cocultured vascular or lymphatic endothelial cells.
Here, we report the first evidence that the atrophic phenotype observed in both muscle obtained from mice bearing the C26 adenocarcinoma and C2C12 myotubes treated with dexamethasone was characterized by reduced levels of active phospho-SphK1.
Strongly positive SK1 staining was found in 21/28 (75%) of rat colon adenocarcinomas induced by AOM, whereas no positive SK1 staining was observed in normal mucosa.
Immunohistochemical screening for SK1 expression was performed in 25 samples of normal/tumor patient matched non-small-cell lung cancer tissue and found that 25 of 25 tumor samples (carcinoid [5 samples], squamous [10 samples], and adenocarcinoma tumors [10 samples]), exhibited overwhelmingly positive immunostaining for SK1 as compared with patient-matched normal tissue.
This study provides a significant understanding of SphK1 inhibitors that can be used in the development of potential therapeutics against breast cancer.
This study provides a significant understanding of SphK1 inhibitors that can be used in the development of potential therapeutics against breast cancer.
GP73-SphK1sR-Ad5 was constructed by integrating Golgi protein 73 (GP73) promoter and sphingosine kinase 1 (SphK1)-short hairpin RNA (shRNA) into adenovirus serotype 5 (Ad5), and transfecting into HCC Huh7 cells and normal human liver HL-7702 cells.
Exosomal transfer of miR-124 inhibits normal fibroblasts to cancer-associated fibroblasts transition by targeting sphingosine kinase 1 in ovarian cancer.
Sphingosine kinase 1 (SphK1) is one of the central enzymes of sphingolipid metabolism whose high expression level is presumed to be correlated with cancer and other inflammatory diseases.
Sphingosine kinase 1 (SPHK1), an ATP-dependent protein, has previously been demonstrated to be upregulated in several types of human cancer and to play an important role in tumor development and progression.
In conclusion, we infer that quercetin and capsaicin provide a chemical scaffold to develop potent and selective inhibitors of SphK1 after required modifications for the clinical management of cancer.
High SPHK1 expression was significantly associated with aggressive CRC behavior and worse overall survival, and was an independent predictor of distant metastasis.
Altogether, our findings suggested a POTEE/SPHK1/p65 signaling axis could promote colorectal tumorigenesis and POTEE might potentially serve as a novel biomarker for the diagnosis and an intervention of colorectal cancer.