ArticleOncotarget2016
Suppression of c-Myc and RRM2 expression in pancreatic cancer cells by the sphingosine kinase-2 inhibitor ABC294640.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 41 citations in OpenAlex.
- Therapeutic potential of the sphingosine kinase 2 inhibitor opaganib.Pharmaceutical science advances · 2026Review
- Targeting sphingosine 1-phosphate and sphingosine kinases in pancreatic cancer: mechanisms and therapeutic potential.Cancer cell international · 2024Review
- Targeting SNAI1-Mediated Colorectal Cancer Chemoresistance and Stemness by Sphingosine Kinase 2 Inhibition.World journal of oncology · 2024Article
- Therapeutic Potential of Ceramide in Cancer Treatment.Journal of cancer research and oncobiology · 2024Article
- Developing new ceramide analogs against non-small cell lung cancer (NSCLC).American journal of cancer research · 2024Article
- Opaganib (ABC294640) Induces Immunogenic Tumor Cell Death and Enhances Checkpoint Antibody Therapy.International journal of molecular sciences · 2023Article
- Opaganib Protects against Radiation Toxicity: Implications for Homeland Security and Antitumor Radiotherapy.International journal of molecular sciences · 2022Article
- Review
- Recent Progress in the Development of Opaganib for the Treatment of Covid-19.Drug design, development and therapy · 2022Review
- The Sphingosine Kinase 2 Inhibitor Opaganib Protects Against Acute Kidney Injury in Mice.International journal of nephrology and renovascular disease · 2022Article
- The Role of Ceramide Metabolism and Signaling in the Regulation of Mitophagy and Cancer Therapy.Cancers · 2021Review
- Targeting the Sphingosine Kinase/Sphingosine-1-Phosphate Signaling Axis in Drug Discovery for Cancer Therapy.Cancers · 2021Review
- Sphingosine 1-phosphate Stimulates Insulin Secretion and Improves Cell Survival by Blocking Voltage-dependent KFrontiers in pharmacology · 2021Article
- Targeting Sphingolipids for Cancer Therapy.Frontiers in oncology · 2021Review
- Sphingosine 1-Phosphate Signaling and Metabolism in Chemoprevention and Chemoresistance in Colon Cancer.Molecules (Basel, Switzerland) · 2020Review
- Metabolic Plasticity in Chemotherapy Resistance.Frontiers in oncology · 2020Review
- Targeting Sphingosine Kinase by ABC294640 against Diffuse Intrinsic Pontine Glioma (DIPG).Journal of Cancer · 2020Article
- A genome-scale CRISPR/Cas9 knockout screening reveals SH3D21 as a sensitizer for gemcitabine.Scientific reports · 2019Article
- Targeting sphingosine kinase 2 suppresses cell growth and synergizes with BCL2/BCL-XL inhibitors through NOXA-mediated MCL1 degradation in cholangiocarcinoma.American journal of cancer research · 2019Article
- Sphingosine kinase 2 inhibitor ABC294640 displays anti-epithelial ovarian cancer activities in vitro and in vivo.OncoTargets and therapy · 2019Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic cancer remains extremely difficult to treat, with the average lifespan following diagnosis being only 3-6 months, resulting in a death to incidence ratio of 0.94. A major reason for this high mortality rate is resistance to the main chemotherapeutic agent used to treat this disease, gemcitabine. Alterations in nucleoside and gemcitabine metabolism, specifically over-expression of ribonucleotide reductase, have been implicated as a major mechanism of resistance to this drug. Here, we show that inhibition of sphingosine kinase-2 by the specific inhibitor ABC294640 is synergistically cytotoxic with gemcitabine toward three human pancreatic cancer cell lines. Treatment with ABC294640 results in decreased expression of both RRM2 and MYC in all three cell lines. Additionally, expression of c-Myc protein and phosphorylation of Rb at S780 both decrease in a dose-dependent manner in response to ABC294640, while acetylation of H3-K9 and p21 levels increase. Pretreatment with the protein phosphatase 1 inhibitor okadaic acid or the ceramide synthase inhibitor fumonisin B1 fails to prevent the effects of ABC294640 on Rb phosphorylation. These data indicate a role for sphingosine kinase-2 in E2F and c-Myc mediated transcription through alteration of histone acetylation and p21 expression. These effects of ABC294640 suggest that it may be an effective agent for pancreatic cancer, particularly in combination with gemcitabine.
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