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.

中文翻译：

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查尔酮甲氧基衍生物对犬淋巴瘤和白血病细胞具有抗增殖和促凋亡活性


查耳酮因其易于合成且具有广泛的生物活性而成为抗癌药物的有趣候选者。该研究展示了新合成的带有甲氧基的查尔酮类似物对一组犬淋巴瘤和白血病细胞系的抗肿瘤活性。采用MTT法评价不同浓度2'-羟基查耳酮及其甲氧基化衍生物作用48 h后的抗增殖作用。通过对用膜联蛋白 V/FITC 和碘化丙啶染色的细胞进行细胞计数分析并通过测量半胱天冬酶 3/7 和 8 激活来研究促凋亡活性。通过磷酸化组蛋白 H2AX 的蛋白质印迹分析评估 DNA 损伤。新化合物对所研究的细胞系具有选择性抗增殖活性，最有效的是2'-羟基-2",5"-二甲氧基查尔酮和2'-羟基-4',6'-二甲氧基查尔酮。 2'-羟基查耳酮和两种最活跃的衍生物诱导细胞凋亡和半胱天冬酶参与，但也观察到一定比例的坏死细胞。比较用不同化合物处理后的磷脂酰丝氨酸外化，注意到添加两个甲氧基增加了促凋亡潜力。即使在对查耳酮诱导的细胞凋亡具有抵抗力的细胞系中，最活跃的化合物也会引发 DNA 损伤。结果证实，这些类似物在治疗犬淋巴瘤或白血病方面具有抗癌潜力。