ArticleInternational journal of biological sciences2022
The sphingosine kinase inhibitor SKI-V suppresses cervical cancer cell growth.
Article in International journal of biological sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 10 citations in OpenAlex.
- Bidirectional mendelian randomization identifies plasma proteins associated with cervical cancer risk.Journal of the Egyptian National Cancer Institute · 2026Article
- Exploring Lipid Metabolic Reprogramming: Mechanistic Insights and Implications for Tumor Radiotherapy.International journal of biological sciences · 2026Review
- PRDM1-driven SLC30A9 overexpression contributes to the malignant phenotype of cervical cancer cells via promoting mitochondrial hyperfunction.Cell death & disease · 2025Article
- Development of a Mitochondrial Permeability Transition-Driven Necrosis-Related Prognostic Signature in Cervical Cancer: Integrating Bulk Transcriptomic and Single-Cell Data.Cancer medicine · 2025Article
- Targeting YTHDF2 inhibits tumorigenesis of diffuse large B-cell lymphoma through ACER2-mediated ceramide catabolism.Journal of advanced research · 2024Article
- Signaling controversy and future therapeutical perspectives of targeting sphingolipid network in cancer immune editing and resistance to tumor necrosis factor-α immunotherapy.Cell communication and signaling : CCS · 2024Review
- Targeting Sphingosine 1-Phosphate Metabolism as a Therapeutic Avenue for Prostate Cancer.Cancers · 2023Review
- MicroRNA-154-5p suppresses cervical carcinoma growth and metastasis by silencing Cullin2PeerJ · 2023Article
- Endothelial cell-specific molecule 1 drives cervical cancer progression.Cell death & disease · 2022Article
- Synthesis of PP2A-Activating PF-543 Derivatives and Investigation of Their Inhibitory Effects on Pancreatic Cancer Cells.Molecules (Basel, Switzerland) · 2022Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Overexpression and/or overactivation of sphingosine kinase 1/2 (SphK1/2) is important for tumorigenesis and progression of cervical cancer. The current study examined the potential activity and signaling mechanisms of SKI-V, a non-lipid small molecule SphK inhibitor, against cervical cancer cells. In different primary and immortalized cervical cancer cells, SKI-V exerted significant anti-cancer activity by inhibiting cell viability, colony formation, proliferation, cell cycle progression and cell migration. Significant apoptosis activation was detected in SKI-V-treated cervical cancer cells. Significantly, SKI-V also provoked programmed necrosis cascade in cervical cancer cells, as it induced mitochondrial p53-cyclophilin-D-adenine nucleotide translocator-1 (ANT1) complexation, mitochondrial membrane potential collapse, reactive oxygen species production and the release of lactate dehydrogenase into the medium. Further, SKI-V blocked SphK activation and induced ceramide accumulation in primary cervical cancer cells, without affecting SphK1/2 expression. SKI-V-induced cytotoxicity in cervical cancer cells was largely inhibited by sphingosine-1-phosphate or the SphK1 activator K6PC-5, but was sensitized by adding the short-chain ceramide C6. Moreover, SKI-V inhibited Akt-mTOR (mammalian target of rapamycin) activation in primary cervical cancer cells, and its cytotoxicity was mitigated by a constitutively-active Akt.
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