Synergistic induction of apoptosis in resistant head and neck carcinoma and leukemia by alkoxyamide-based histone deacetylase inhibitors
| Autor: | Finn K. Hansen, Christian Schrenk, Thomas Kurz, Melf Sönnichsen, Arndt Borkhardt, Sanil Bhatia, Matthias U. Kassack, Alexandra Hamacher, Julian Schliehe-Diecks, Leandro A. Alves Avelar |
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| Rok vydání: | 2020 |
| Předmět: |
Epigenomics
Combination therapy Antineoplastic Agents Apoptosis 01 natural sciences 03 medical and health sciences chemistry.chemical_compound Drug Discovery medicine Humans Epigenetics Vorinostat 030304 developmental biology Pharmacology Cisplatin 0303 health sciences Leukemia 010405 organic chemistry Chemistry Bortezomib Organic Chemistry Drug Synergism General Medicine medicine.disease Carfilzomib 0104 chemical sciences Histone Deacetylase Inhibitors Head and Neck Neoplasms Cancer research Histone deacetylase medicine.drug |
| Zdroj: | European journal of medicinal chemistry. 211 |
| ISSN: | 1768-3254 |
| Popis: | Targeting epigenetic dysregulation has emerged as a valuable therapeutic strategy in cancer treatment. Especially epigenetic combination therapy of histone deacetylase inhibitors (HDACi) with established anti-cancer drugs has provided promising results in preclinical and clinical studies. The structural optimization of alkoxyamide-based class I/IIb inhibitors afforded improved analogs with potent efficacy in cisplatin-resistant head and neck carcinoma cells and bortezomib-resistant leukemia cells. The most promising HDACi showed a superior synergistic cytotoxic activity as compared to vorinostat and class I HDACi in combination with cisplatin, leading to a full reversal of the chemoresistant phenotype in head and neck cancer cell lines, as well in combination with the proteasome inhibitors (bortezomib and carfilzomib) in a panel of leukemic cell lines. Furthermore, the most valuable alkoxyamide-based HDACi exhibited strong ex vivo anticancer efficacy against primary patient samples obtained from different therapy-resistant leukemic entities. |
| Databáze: | OpenAIRE |
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