ArticleBiochimica et biophysica acta2009
Downregulation of neutral ceramidase by gemcitabine: Implications for cell cycle regulation.
Article in Biochimica et biophysica acta, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 42 citations in OpenAlex.
- The Role of Ceramide and Sphingolipid Metabolism in Cancer Therapeutics.Journal of oncology research and therapy · 2024Article
- Transcriptomics of mussel transmissible cancer MtrBTN2 suggests accumulation of multiple cancer traits and oncogenic pathways shared among bilaterians.Open biology · 2023Article
- Measurement of neutral ceramidase activity in vitro and in vivo.Analytical biochemistry · 2022Review
- Ceramide synthase 2-CFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Approaches for probing and evaluating mammalian sphingolipid metabolism.Analytical biochemistry · 2019Review
- Overexpression of acid ceramidase (ASAH1) protects retinal cells (ARPE19) from oxidative stress.Journal of lipid research · 2019Article
- Neutral ceramidase: Advances in mechanisms, cell regulation, and roles in cancer.Advances in biological regulation · 2019Review
- Essential Oil from Carpesium abrotanoides L. Induces Apoptosis via Activating Mitochondrial Pathway in Hepatocellular Carcinoma Cells.Current medical science · 2018Article
- Functions of neutral ceramidase in the Golgi apparatus.Journal of lipid research · 2018Article
- AKT as a key target for growth promoting functions of neutral ceramidase in colon cancer cells.Oncogene · 2018Article
- Sphingolipids and their metabolism in physiology and disease.Nature reviews. Molecular cell biology · 2018Review
- Ceramidases, roles in sphingolipid metabolism and in health and disease.Advances in biological regulation · 2017Review
- Role of neutral ceramidase in colon cancer.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016Article
- Alkaline ceramidase 2 and its bioactive product sphingosine are novel regulators of the DNA damage response.Oncotarget · 2016Article
- Structural Basis for Ceramide Recognition and Hydrolysis by Human Neutral Ceramidase.Structure (London, England : 1993) · 2015Article
- Sphingolipids in the DNA damage response.Advances in biological regulation · 2015Review
- Evolving concepts in cancer therapy through targeting sphingolipid metabolism.Biochimica et biophysica acta · 2014Review
- Purification and biochemical characterization of membrane-bound neutral ceramidase from camel brain (Camelus dromedarius).International journal of biochemistry and molecular biology · 2013Article
- Loss of neutral ceramidase increases inflammation in a mouse model of inflammatory bowel disease.Prostaglandins & other lipid mediators · 2012Article
- Acid ceramidase (ASAH1) is a global regulator of steroidogenic capacity and adrenocortical gene expression.Molecular endocrinology (Baltimore, Md.) · 2012Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Gemcitabine (GMZ) is a chemotherapeutic agent with well established effects on cell growth arrest and apoptosis. In this study, we investigated the potential roles of bioactive sphingolipids in mediating the growth suppressing effects of GMZ on a polyoma middle T transformed murine endothelial cell line. After 12-hour GMZ (0.6 microM) treatment, cell growth was arrested at the G(0)/G(1) phase as detected by flow cytometric cell cycle analysis and MTT cell viability analysis, and this was accompanied by dephosphorylation of the retinoblastoma protein (Rb). Furthermore, GMZ treatment resulted in increased levels of specifically the very long chain ceramides as determined by mass spectrometry. Mechanistically, GMZ did not appear to affect the activities of many enzymes of ceramide metabolism; however, GMZ caused a selective reduction in the protein levels of neutral ceramidase (NCDase), as indicated by Western blot analysis, with a concomitant decrease in NCDase activity. The significance of NCDase loss on cell cycle regulation was investigated by specific knockdown of the enzyme using small interfering RNA (siRNA). Interestingly, NCDase siRNA transfection was sufficient to induce a cell cycle arrest at G(0)/G(1) and an increase in total ceramide levels, with significant elevation in very long chain ceramides (C(24:1) and C(24:0)). NCDase siRNA also induced Rb dephosphorylation. These data provide evidence for a novel mechanism of action for GMZ and highlight downregulation of NCDase as a critical step in GMZ-mediated ceramide elevation and cell cycle arrest.
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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.