Departamento de Bioquímica y Biología Molecular, Unidad Asociada al Consejo Superior de Investigaciones Científicas (CSIC), Instituto Canario de Investigación del Cáncer, Universidad de Las Palmas de Gran Canaria, Plaza Dr. Pasteur s/n, 35016 Las Palmas de Gran Canaria, Spain.
Instituto Productos Naturales y Agrobiología, CSIC, Avenida Astrofísico Francisco Sánchez 3, 38206 La Laguna, Tenerife, Spain.
Eur J Med Chem. 2014 Sep 12;84:30-41. doi: 10.1016/j.ejmech.2014.07.010. Epub 2014 Jul 4.
Flavonoids are polyphenolic compounds which display an array of biological activities and are considered potential antitumor agents. Here we evaluated the antiproliferative activity of selected synthetic flavonoids against human leukemia cell lines. We found that 4'-bromoflavonol (flavonol 3) was the most potent. This compound inhibited proliferation in a concentration-dependent manner, induced apoptosis and blocked cell cycle progression at the S phase. Cell death was found to be associated with the cleavage and activation of multiple caspases, the activation of the mitogen-activated protein kinase pathway and the up-regulation of two death receptors (death receptor 4 and death receptor 5) for tumor necrosis factor-related apoptosis-inducing ligand. Moreover, combined treatments using 4'-bromoflavonol and TRAIL led to an increased cytotoxicity compared to single treatments. These results provide a basis for further exploring the potential applications of this combination for the treatment of cancer.
类黄酮是具有多种生物活性的多酚化合物，被认为是潜在的抗肿瘤药物。在这里，我们评估了选定的合成类黄酮对人白血病细胞系的增殖抑制活性。我们发现 4'-溴黄酮醇（黄酮醇 3）是最有效的。该化合物以浓度依赖的方式抑制增殖，诱导细胞凋亡并阻断 S 期的细胞周期进程。细胞死亡与多种半胱天冬酶的切割和激活、丝裂原活化蛋白激酶途径的激活以及两种肿瘤坏死因子相关凋亡诱导配体的死亡受体（死亡受体 4 和死亡受体 5）的上调有关。此外，与单独治疗相比，使用 4'-溴黄酮醇和 TRAIL 的联合治疗导致细胞毒性增加。这些结果为进一步探索这种组合在癌症治疗中的潜在应用提供了基础。
