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

Aleksandra Pawlak,Bożena Obmińska-Mrukowicz,Ewa Kozłowska,Beatriz Hernández Suárez,Mateusz Łużny,Marta Henklewska,Tomasz Janeczko

doi:10.3390/molecules25194362

Aleksandra Pawlak, Bożena Obmińska-Mrukowicz + Show 5 more

Open Access

https://doi.org/10.3390/molecules25194362

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Abstract

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.

Highlights

The search for novel natural or synthetic compounds with potential antitumor activity is one of the major goals of contemporary oncology
An assay was performed to determine whether the tested chalcones have antiproliferative activity against normal cells, and if the position of the substituents in the structure has an influence on the potency of such effects
Modification of the chemical structure of 20 -hydroxychalcone leads to the formation of a derivatives with various antitumor activity in vitro

Summary

Introduction

The search for novel natural or synthetic compounds with potential antitumor activity is one of the major goals of contemporary oncology The research involves both known compounds with proven biological activity as well as newly synthesized molecules that are structural analogues of biologically active substances already used in the treatment of cancer. Molecules 2020, 25, 4362 on a combination of drugs with various molecular mechanisms of action and different side effects With regard to this principle, research focusing on the antitumor activity of new natural compounds or their derivatives is highly justified. Such a potentially interesting group of compounds may be chalcones, an essential group of natural compounds classified as flavonoids [1] Their typical structural feature is an open, α,β-unsaturated three-carbon fragment connecting two aromatic rings [2]. They are yellow [3] and commonly occur in the world of plants: in citrus fruits, vegetables and spices [4,5]

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