A metal-free salalen ligand with anti-tumor and synergistic activity in resistant leukemia and solid tumor cells via mitochondrial pathway
| Autor: | Nicola L Wilke, Qifang Wang, Nathalie Wilke, Marie Ahrweiler, Sina M. Hopff, Albrecht Berkessel, Aram Prokop, Corazon Frias |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cancer Research Vincristine medicine.medical_specialty Antineoplastic Agents Apoptosis Multidrug resistance Ligands Metal-free ligand Synergistic effects 03 medical and health sciences 0302 clinical medicine Western blot Neoplasms Internal medicine Tumor Cells Cultured medicine Humans Caspase Polymerase Cell Proliferation Leukemia Hematology biology medicine.diagnostic_test Chemistry Mitochondrial pathway Drug Synergism General Medicine Ligand (biochemistry) medicine.disease Drug Resistance Multiple Mitochondria 030104 developmental biology Oncology Drug Resistance Neoplasm Salalen 030220 oncology & carcinogenesis biology.protein Cancer research Cisplatin Original Article – Cancer Research medicine.drug |
| Zdroj: | Journal of Cancer Research and Clinical Oncology |
| ISSN: | 1432-1335 0171-5216 |
| Popis: | Purpose Since the discovery of the well-known cis-platin, transition metal complexes are highly recognized as cytostatic agents. However, toxic side effects of the metal ions present in the complexes may pose significant problems for their future development. Therefore, we investigated the metal-free salalen ligand WQF 044. Methods DNA fragmentations in leukemia (Nalm6) and solid tumor cells (BJAB, MelHO, MCF-7, RM82) proved the apoptotic effects of WQF 044, its overcoming of resistances and the cellular pathways that are affected by the substance. The apoptotic mechanisms finding were supported by western blot analysis, measurement of the mitochondrial membrane potential and polymerase chain reactions. Results A complex intervention in the mitochondrial pathway of apoptosis with a Bcl-2 and caspase dependence was observed. Additionally, a wide range of tumors were affected by the ligand in a low micromolar range in-vitro. The compound overcame multidrug resistances in P-gp over-expressed acute lymphoblastic leukemia and CD95-downregulated Ewing’s sarcoma cells. Quite remarkable synergistic effects with vincristine were observed in Burkitt-like lymphoma cells. Conclusion The investigation of a metal-free salalen ligand as a potential anti-cancer drug revealed in promising results for a future clinical use. |
| Databáze: | OpenAIRE |
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