Cargando…

Chalcone Methoxy Derivatives Exhibit Antiproliferative and Proapoptotic Activity on Canine Lymphoma and Leukemia Cells

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 antipro...

Descripción completa

Detalles Bibliográficos
Autores principales: Pawlak, Aleksandra, Henklewska, Marta, Hernández Suárez, Beatriz, Łużny, Mateusz, Kozłowska, Ewa, Obmińska-Mrukowicz, Bożena, Janeczko, Tomasz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582533/
https://www.ncbi.nlm.nih.gov/pubmed/32977440
http://dx.doi.org/10.3390/molecules25194362
_version_ 1783599213829947392
author Pawlak, Aleksandra
Henklewska, Marta
Hernández Suárez, Beatriz
Łużny, Mateusz
Kozłowska, Ewa
Obmińska-Mrukowicz, Bożena
Janeczko, Tomasz
author_facet Pawlak, Aleksandra
Henklewska, Marta
Hernández Suárez, Beatriz
Łużny, Mateusz
Kozłowska, Ewa
Obmińska-Mrukowicz, Bożena
Janeczko, Tomasz
author_sort Pawlak, Aleksandra
collection PubMed
description 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′-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′-hydroxy-2″,5″-dimethoxychalcone and 2′-hydroxy-4′,6′-dimethoxychalcone. 2′-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.
format Online
Article
Text
id pubmed-7582533
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-75825332020-10-29 Chalcone Methoxy Derivatives Exhibit Antiproliferative and Proapoptotic Activity on Canine Lymphoma and Leukemia Cells Pawlak, Aleksandra Henklewska, Marta Hernández Suárez, Beatriz Łużny, Mateusz Kozłowska, Ewa Obmińska-Mrukowicz, Bożena Janeczko, Tomasz Molecules Article 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′-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′-hydroxy-2″,5″-dimethoxychalcone and 2′-hydroxy-4′,6′-dimethoxychalcone. 2′-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. MDPI 2020-09-23 /pmc/articles/PMC7582533/ /pubmed/32977440 http://dx.doi.org/10.3390/molecules25194362 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pawlak, Aleksandra
Henklewska, Marta
Hernández Suárez, Beatriz
Łużny, Mateusz
Kozłowska, Ewa
Obmińska-Mrukowicz, Bożena
Janeczko, Tomasz
Chalcone Methoxy Derivatives Exhibit Antiproliferative and Proapoptotic Activity on Canine Lymphoma and Leukemia Cells
title Chalcone Methoxy Derivatives Exhibit Antiproliferative and Proapoptotic Activity on Canine Lymphoma and Leukemia Cells
title_full Chalcone Methoxy Derivatives Exhibit Antiproliferative and Proapoptotic Activity on Canine Lymphoma and Leukemia Cells
title_fullStr Chalcone Methoxy Derivatives Exhibit Antiproliferative and Proapoptotic Activity on Canine Lymphoma and Leukemia Cells
title_full_unstemmed Chalcone Methoxy Derivatives Exhibit Antiproliferative and Proapoptotic Activity on Canine Lymphoma and Leukemia Cells
title_short Chalcone Methoxy Derivatives Exhibit Antiproliferative and Proapoptotic Activity on Canine Lymphoma and Leukemia Cells
title_sort chalcone methoxy derivatives exhibit antiproliferative and proapoptotic activity on canine lymphoma and leukemia cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582533/
https://www.ncbi.nlm.nih.gov/pubmed/32977440
http://dx.doi.org/10.3390/molecules25194362
work_keys_str_mv AT pawlakaleksandra chalconemethoxyderivativesexhibitantiproliferativeandproapoptoticactivityoncaninelymphomaandleukemiacells
AT henklewskamarta chalconemethoxyderivativesexhibitantiproliferativeandproapoptoticactivityoncaninelymphomaandleukemiacells
AT hernandezsuarezbeatriz chalconemethoxyderivativesexhibitantiproliferativeandproapoptoticactivityoncaninelymphomaandleukemiacells
AT łuznymateusz chalconemethoxyderivativesexhibitantiproliferativeandproapoptoticactivityoncaninelymphomaandleukemiacells
AT kozłowskaewa chalconemethoxyderivativesexhibitantiproliferativeandproapoptoticactivityoncaninelymphomaandleukemiacells
AT obminskamrukowiczbozena chalconemethoxyderivativesexhibitantiproliferativeandproapoptoticactivityoncaninelymphomaandleukemiacells
AT janeczkotomasz chalconemethoxyderivativesexhibitantiproliferativeandproapoptoticactivityoncaninelymphomaandleukemiacells