Grupo de Investigaciones Biomédicas y de Genética Humana Aplicada (GIBGA), Laboratorio de Biología Celular y Molecular, Facultad de Ciencias de la Salud, Universidad de Ciencias Aplicadas y Ambientales (U.D.C.A), Calle 222 # 55-37, Bogotá 111321, Colombia.
Grupo de Investigación en Productos Naturales (PRONAUDCA), Laboratorio de Productos Naturales, Facultad de Ciencias, Universidad de Ciencias Aplicadas y Ambientales (U.D.C.A), Calle 222 # 55-37, Bogotá 111321, Colombia.
Molecules. 2022 Dec 21;28(1):58. doi: 10.3390/molecules28010058.
is a source of flavonoids with antiproliferative properties in human breast cancer cells, the most common neoplasm diagnosed in patients worldwide. Until now, the mechanisms of cell death related to the antiproliferative activity of its flavonoids have not been elucidated. In this study, a novel flavanone (3',4'-dihydroxy-5,7-dimethoxy-flavanone) was isolated from the plant leaves and identified by nuclear magnetic resonance (NMR) and mass spectrometry (MS). This molecule selectively inhibited cell proliferation of triple-negative human breast cancer cell lines MDA-MB-231 and MCF-7 whit IC values of 25.3 μg/mL and 20.8 μg/mL, respectively, determined by MTT assays with a selectivity index greater than 3. Early and late pro-apoptotic characteristics were observed by annexin-V/7-AAD detection, accompanied by a high percentage of the Bcl-2 anti-apoptotic protein inactivated and the activation of effector Caspase-3 and/or 7 in breast cancer cells. It was verified the decreasing of XIAP more than Bcl-2 anti-apoptotic proteins expression, as well as the XIAP/Caspase-7 and Bcl-2/Bax complexes dissociation after flavanone treatment. Docking and molecular modeling analysis between the flavanone and the antiapoptotic protein XIAP suggests that the natural compound inhibits XIAP by binding to the BIR3 domain of XIAP. In this case, we demonstrate that the new flavanone isolated from leaves of has a promising and selective anti-breast cancer potential that includes the induction of intrinsic apoptosis by downregulation of the anti-apoptotic proteins XIAP and Bcl-2. New studies should deepen these findings to demonstrate its potential as an anticancer agent.
是一种具有抗人类乳腺癌细胞增殖特性的类黄酮来源，乳腺癌是全球患者最常见的肿瘤。到目前为止，其类黄酮的抗增殖活性相关的细胞死亡机制尚未阐明。在这项研究中，从植物叶子中分离出一种新型的黄烷酮（3'，4'-二羟基-5,7-二甲氧基黄烷酮），并通过核磁共振（NMR）和质谱（MS）鉴定。该分子选择性地抑制三阴性人乳腺癌细胞系 MDA-MB-231 和 MCF-7 的细胞增殖，IC 值分别为 25.3 μg/mL 和 20.8 μg/mL，这是通过 MTT 测定法确定的，其选择性指数大于 3。通过 Annexin-V/7-AAD 检测观察到早期和晚期促凋亡特征，伴随着 Bcl-2 抗凋亡蛋白的高比例失活和效应 Caspase-3 和/或 7 在乳腺癌细胞中的激活。验证了在黄烷酮处理后，XIAP 的表达降低超过 Bcl-2 抗凋亡蛋白的表达，以及 XIAP/Caspase-7 和 Bcl-2/Bax 复合物的解离。黄烷酮与抗凋亡蛋白 XIAP 之间的对接和分子建模分析表明，天然化合物通过与 XIAP 的 BIR3 结构域结合来抑制 XIAP。在这种情况下，我们证明了从叶子中分离出的新型黄烷酮具有有希望的和选择性的抗乳腺癌潜力，包括通过下调抗凋亡蛋白 XIAP 和 Bcl-2 诱导内在凋亡。应进行新的研究以证明其作为抗癌剂的潜力。
