ArticleJournal of experimental & clinical cancer research : CR2022
Inhibition of carbonic anhydrases IX/XII by SLC-0111 boosts cisplatin effects in hampering head and neck squamous carcinoma cell growth and invasion.
Article in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 94 citations in OpenAlex.
- Design and Synthesis of Bis-Triazole-Linked Benzenesulfonamides as Selective Carbonic Anhydrase IX/XII Inhibitors with Chemosensitizing Activity.Journal of medicinal chemistry · 2026Article
- Establishment, validation and application of a spectrophotometric method for the accurate determination of carbonic anhydrase activity.RSC advances · 2025Article
- Article
- Review
- Multifaceted Sulfonamide-Derived Thiosemicarbazones: Combining Metal Chelation and Carbonic Anhydrases Inhibition in Anticancer Therapy.International journal of molecular sciences · 2025Article
- Novel 3-Sulfonamide Dual-Tail Pyrrol-2-one Bridged Molecules as Potent Human Carbonic Anhydrase Isoform Inhibitors: Design, Synthesis, Molecular Modeling Investigation, and Anticancer Activity in MeWo, SK-BR-3, and MG-63 Cell Lines.Journal of medicinal chemistry · 2025Article
- Article
- Discovery of a novel 4-pyridyl SLC-0111 analog targeting tumor-associated carbonic anhydrase isoform IX through tail-based design approach with potent anticancer activity.Frontiers in chemistry · 2025Article
- Different hypoxic response of humanTurkish journal of biology = Turk biyoloji dergisi · 2025Article
- Harnessing Natural Products to Surmount Drug Resistance in Gastric Cancer: Mechanisms and Therapeutic Perspectives.International journal of biological sciences · 2025Review
- The IL-10/STAT3 Axis Nasopharyngeal Carcinoma Cancer stem cell and radio resistance.Scientific reports · 2024Article
- Development of a multi-targeted chemotherapeutic approach based on G-quadruplex stabilisation and carbonic anhydrase inhibition.Journal of enzyme inhibition and medicinal chemistry · 2024Article
- Hydrogen Sulfide-Releasing Carbonic Anhydrase Inhibitors Effectively Suppress Cancer Cell Growth.International journal of molecular sciences · 2024Article
- Identification and characterization of a new potent inhibitor targeting CtBP1/BARS in melanoma cells.Journal of experimental & clinical cancer research : CR · 2024Article
- LncRNA ZNF674-AS1 drives cell growth and inhibits cisplatin-induced pyroptosis via up-regulating CA9 in neuroblastoma.Cell death & disease · 2024Article
- Thiosemicarbazone-benzenesulfonamide Derivatives as Human Carbonic Anhydrases Inhibitors: Synthesis, Characterization, andAnti-cancer agents in medicinal chemistry · 2024Article
- Design and synthesis of some new benzoylthioureido benzenesulfonamide derivatives and their analogues as carbonic anhydrase inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- A novel hypoxia-associated gene signature for prognosis prediction in head and neck squamous cell carcinoma.BMC oral health · 2023Article
- Article
- CAXII inhibitors: Potential sensitizers for immune checkpoint inhibitors in HCC treatment.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundHypoxic tumor microenvironment (TME) contributes to the onset of many aspects of the cancer biology associated to the resistance to conventional therapies. Hypoxia is a common characteristic and negative prognostic factor in the head and neck squamous carcinomas (HNSCC) and is correlated with aggressive and invasive phenotype as well as with failure to chemo- and radio-therapies. The carbonic anhydrase isoenzymes IX and XII (CA IX/XII), regulators of extra and intracellular pH, are overexpressed in TME and are involved in adaptative changes occurring in cancer cells to survive at low O
methodsThe effects of cisplatin, CA IX/XII specific inhibitor SLC-0111, and the combinatorial treatment were tested on proliferation, migration, invasion of HNSCC cells grown in 2D and 3D models. Main signal pathways and the expression of stemness, mesenchymal and apoptotic markers were analyzed by western blotting. Molecular imaging using NIR-Annexin V and NIR-Prosense was performed in HNSCC xenografts to detect tumor growth and metastatic spread.
resultsHNSCC cells grown in 2D and 3D models under hypoxic conditions showed increased levels of CA IX/XII and greater resistance to cisplatin than cells grown under normoxic conditions. The addition of CA IX/XII inhibitor SLC-0111 to cisplatin sensitized HNSCC cells to the chemotherapeutic agent and caused a reduction of proliferation, migration and invasiveness. Furthermore, the combination therapy hampered activation of STAT3, AKT, ERK, and EMT program, whereas it induced apoptosis. In HNSCC xenografts the treatment with cisplatin plus SLC-0111 caused an inhibition of tumor growth and an induction of apoptosis as well as a reduction of metastatic spread at a higher extent than single agents.
conclusionOur results highlight the ability of SLC-0111 to sensitize HNSCC to cisplatin by hindering hypoxia-induced signaling network that are shared among mechanisms involved in therapy resistance and metastasis.
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