ArticleJournal of experimental & clinical cancer research : CR2015
The kinase inhibitor D11 induces caspase-mediated cell death in cancer cells resistant to chemotherapeutic treatment.
Article in Journal of experimental & clinical cancer research : CR, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- Protein kinase CK2 sustains de novo fatty acid synthesis by regulating the expression of SCD-1 in human renal cancer cells.Cancer cell international · 2024Article
- Discovery of 7,9-Dibromo-dihydrodibenzofuran as a Potent Casein Kinase 2 (CK2) Inhibitor: Synthesis, Biological Evaluation, and Structural Studies onACS pharmacology & translational science · 2024Article
- A review on potential heterocycles for the treatment of glioblastoma targeting receptor tyrosine kinases.Oncology research · 2024Review
- Exploration of anti-leukemic effect of soft coral-derived 13-acetoxysarcocrassolide: Induction of apoptosis via oxidative stress as a potent inhibitor of heat shock protein 90 and topoisomerase II.The Kaohsiung journal of medical sciences · 2023Article
- Glioblastoma: Current Status, Emerging Targets, and Recent Advances.Journal of medicinal chemistry · 2022Review
- Review
- Role of Protein Kinase CK2 in Aberrant Lipid Metabolism in Cancer.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Article
- Role of protein kinase CK2 in antitumor drug resistance.Journal of experimental & clinical cancer research : CR · 2019Review
- Natural Compounds and Derivatives as Ser/Thr Protein Kinase Modulators and Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2019Review
- A π-Halogen Bond of Dibenzofuranones with the Gatekeeper Phe113 in Human Protein Kinase CK2 Leads to Potent Tight Binding Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2018Article
- Protein kinase CK2 regulates redox homeostasis through NF-κB and Bcl-xL in cardiomyoblasts.Molecular and cellular biochemistry · 2017Article
- The small-molecule kinase inhibitor D11 counteracts 17-AAG-mediated up-regulation of HSP70 in brain cancer cells.PloS one · 2017Article
- D11-Mediated Inhibition of Protein Kinase CK2 Impairs HIF-1α-Mediated Signaling in Human Glioblastoma Cells.Pharmaceuticals (Basel, Switzerland) · 2017Article
- Simultaneous blockade of interacting CK2 and EGFR pathways by tumor-targeting nanobioconjugates increases therapeutic efficacy against glioblastoma multiforme.Journal of controlled release : official journal of the Controlled Release Society · 2016Article
- Nerve growth factor: role in growth, differentiation and controlling cancer cell development.Journal of experimental & clinical cancer research : CR · 2016Review
- Protein Kinase CK2: A Targetable BCR-ABL Partner in Philadelphia Positive Leukemias.Advances in hematology · 2015Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMulti-drug resistance and predisposition to metastasize are major clinical problems in cancer treatment. Malignant primary brain tumor and pancreatic cancer are two well-known examples of malignant tumors resistant to conventional therapies where aberrant EGFR-mediated and NF-κB signal transduction pathways are likely to play an important role. We have recently identified 1,3-Dichloro-6-[(E)-((4-methoxyphenyl)imino)methyl] diben-zo(b,d) furan-2,7-diol (D11) as a potent and selective inhibitor of CK2 a serine/threonine protein kinase that modulates the aforementioned signaling cascades.
methodsHuman cancer cell lines (glioblastoma and pancreatic adenocarcinoma) resistant to conventional chemotherapeutic agents were incubated with increasing concentrations of D11 for variable amounts of time. Cell viability, cell death and effects on major signal transduction pathways deregulated in cancer cells were analyzed by ELISA, FACS and Western blot-based assays, respectively. Moreover, effects on cell migration and in cell protein-protein association were investigated by wound-healing and in situ proximity ligation assays, respectively.
resultsWe show here, that D11 treatment leads to i) significant caspase-mediated apoptotic cell death, ii) down-regulation of EGFR expression and iii) inhibition of NF-κB transcriptional activity. Furthermore, cell exposure to D11 results in impaired cell migration and correlates with reduced expression of the ion co-transporter and cell volume regulator Na(+)-K(+)-2Cl(-) (NKCC1).
conclusionsData reported here underline the therapeutic potential of D11 with respect to certain types of cancer that carry aberrant intracellular signaling cascades and/or exhibit sustained cell migration and suggest a new therapeutic strategy against chemotherapy resistance.
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