ArticleCell death & disease2022
Targeting sphingosine kinase 1/2 by a novel dual inhibitor SKI-349 suppresses non-small cell lung cancer cell growth.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 36 citations in OpenAlex.
- Estradiol Promotes Tumor Progression in ERα-Low Endometrial Cancer via the GPER/SphK1 Pathway.Journal of biochemical and molecular toxicology · 2026Article
- Distinct metabolic profiles in lung adenocarcinomas presenting as solid or ground-glass opacities.NPJ precision oncology · 2026Article
- Exploring mitochondrial ribosomal protein S12 as a novel target for non-small cell lung cancer.NPJ precision oncology · 2025Article
- Sphingolipid metabolism dysregulation: A cause for lung cancer development, progression, and resistance to therapies.Chinese medical journal pulmonary and critical care medicine · 2025Review
- NADH:ubiquinone oxidoreductase core subunit S8 expression and functional significance in non-small cell lung cancer.Cell death & disease · 2025Article
- The expression and functional role of proline-rich 15 in non-small cell lung cancer.Cell death & disease · 2025Article
- Exploring Disparities in Gill Physiological Responses to NaHCOMetabolites · 2024Article
- Targeting POLRMT by IMT1 inhibits colorectal cancer cell growth.Cell death & disease · 2024Article
- Increased expression of REG3A promotes tumorigenic behavior in triple negative breast cancer cells.Breast cancer research : BCR · 2024Article
- MicroRNA Monitoring in Human Alveolar Macrophages from Patients with Smoking-Related Lung Diseases: A Preliminary Study.Biomedicines · 2024Article
- Article
- Developing new ceramide analogs against non-small cell lung cancer (NSCLC).American journal of cancer research · 2024Article
- Targeting SphK1/2 by SKI-178 inhibits prostate cancer cell growth.Cell death & disease · 2023Article
- Targeting Sphingosine 1-Phosphate Metabolism as a Therapeutic Avenue for Prostate Cancer.Cancers · 2023Review
- A first-in-class HBO1 inhibitor WM-3835 inhibits castration-resistant prostate cancer cell growth in vitro and in vivo.Cell death & disease · 2023Article
- miR-19a mediates the mechanism by which SPHK2 regulates hypopharyngeal squamous cell carcinoma progression through the PI3K/AKT axis.American journal of cancer research · 2023Article
- Recent progress in targeted therapy for non-small cell lung cancer.Frontiers in pharmacology · 2023Review
- Identification of the mitochondrial protein ADCK2 as a therapeutic oncotarget of NSCLC.International journal of biological sciences · 2022Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sphingosine kinase 1 (SphK1) and sphingosine kinase (SphK2) are both important therapeutic targets of non-small cell lung cancer (NSCLC). SKI-349 is a novel, highly efficient and small molecular SphK1/2 dual inhibitor. Here in primary human NSCLC cells and immortalized cell lines, SKI-349 potently inhibited cell proliferation, cell cycle progression, migration and viability. The dual inhibitor induced mitochondrial depolarization and apoptosis activation in NSCLC cells, but it was non-cytotoxic to human lung epithelial cells. SKI-349 inhibited SphK activity and induced ceramide accumulation in primary NSCLC cells, without affecting SphK1/2 expression. SKI-349-induced NSCLC cell death was attenuated by sphingosine-1-phosphate and by the SphK activator K6PC-5, but was potentiated by the short-chain ceramide C6. Moreover, SKI-349 induced Akt-mTOR inactivation, JNK activation, and oxidative injury in primary NSCLC cells. In addition, SKI-349 decreased bromodomain-containing protein 4 (BRD4) expression and downregulated BRD4-dependent genes (Myc, cyclin D1 and Klf4) in primary NSCLC cells. At last, SKI-349 (10 mg/kg) administration inhibited NSCLC xenograft growth in nude mice. Akt-mTOR inhibition, JNK activation, oxidative injury and BRD4 downregulation were detected in SKI-349-treated NSCLC xenograft tissues. Taken together, targeting SphK1/2 by SKI-349 potently inhibits NSCLC cell growth in vitro and in vivo.
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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 Socratic graph.