Chalcone Methoxy Derivatives Exhibit Antiproliferative and Proapoptotic Activity on Canine Lymphoma and Leukemia Cells
| Autor: | Bożena Obmińska-Mrukowicz, Beatriz Hernández Suárez, Ewa Kozłowska, Tomasz Janeczko, Aleksandra Pawlak, Marta Henklewska, Mateusz Łużny |
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| Rok vydání: | 2020 |
| Předmět: |
Chalcone
Lymphoma DNA damage Pharmaceutical Science Antineoplastic Agents 01 natural sciences Article Analytical Chemistry lcsh:QD241-441 Inhibitory Concentration 50 03 medical and health sciences chemistry.chemical_compound Dogs lcsh:Organic chemistry Cell Line Tumor Drug Discovery Animals MTT assay Propidium iodide Physical and Theoretical Chemistry canine cancer cell lines Caspase Cell Proliferation 030304 developmental biology 0303 health sciences Canine Lymphoma Leukemia Dose-Response Relationship Drug biology chalcones 010405 organic chemistry Chemistry Organic Chemistry apoptosis Biological activity Molecular biology 0104 chemical sciences anticancer activity Chemistry (miscellaneous) Apoptosis biology.protein Molecular Medicine Drug Screening Assays Antitumor |
| Zdroj: | Molecules Volume 25 Issue 19 Molecules, Vol 25, Iss 4362, p 4362 (2020) |
| ISSN: | 1420-3049 |
| Popis: | Chalcones are interesting candidates for anti-cancer drugs due to the ease of their synthesis and their extensive biological activity. The study presents antitumor activity of newly synthesized chalcone analogues with a methoxy group on a panel of canine lymphoma and leukemia cell lines. The antiproliferative effect of the 2&prime hydroxychalcone and its methoxylated derivatives was evaluated in MTT assay after 48 h of treatment in different concentrations. The proapoptotic activity was studied by cytometric analysis of cells stained with Annexin V/FITC and propidium iodide and by measure caspases 3/7 and 8 activation. The DNA damage was evaluated by Western blot analysis of phosphorylated histone H2AX. The new compounds had selective antiproliferative activity against the studied cell lines, the most effective were the 2&prime hydroxy-2&Prime 5&Prime dimethoxychalcone and 2&prime hydroxy-4&prime 6&prime dimethoxychalcone. 2&prime Hydroxychalcone and the two most active derivatives induced apoptosis and caspases participation, but some percentage of necrotic cells was also observed. Comparing phosphatidylserine externalization after treatment with the different compounds it was noted that the addition of two methoxy groups increased the proapoptotic potential. The most active compounds triggered DNA damage even in the cell lines resistant to chalcone-induced apoptosis. The results confirmed that the analogues could have anticancer potential in the treatment of canine lymphoma or leukemia. |
| Databáze: | OpenAIRE |
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