Mendez-Callejas Gina, Piñeros-Avila Marco, Celis Crispin A, Torrenegra Ruben, Espinosa-Benitez Anderson, Pestana-Nobles Roberto, Yosa-Reyes Juvenal
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 111166, Colombia.
Grupo de Investigación en Fitoquímica (GIFUJ), Departamento de Química, Facultad de Ciencias, Pontificia Universidad Javeriana, Cra. 7 #40-62, Bogotá 111321, Colombia.
Plants (Basel). 2024 Feb 20;13(5):570. doi: 10.3390/plants13050570.
Breast cancer (BC) is one of the most common cancers among women. Effective treatment requires precise tailoring to the genetic makeup of the cancer for improved efficacy. Numerous research studies have concentrated on natural compounds and their anti-breast cancer properties to improve the existing treatment options. (Klatt) R.M. King and H. Rob (. is a notable source of bioactive hydroxy-methylated flavonoids. However, the specific anti-BC mechanisms of these flavonoids, particularly those present in the plant's inflorescences, remain partly undefined. This study focuses on assessing a chalcone derivative extracted from inflorescences for its potential to concurrently activate regulated autophagy and intrinsic apoptosis in luminal A and triple-negative BC cells. We determined the chemical composition of the chalcone using ultraviolet (UV) and nuclear magnetic resonance (NMR) spectroscopy. Its selective cytotoxicity against BC cell lines was assessed using the MTT assay. Flow cytometry and Western blot analysis were employed to examine the modulation of proteins governing autophagy and the intrinsic apoptosis pathway. Additionally, in silico simulations were conducted to predict interactions between chalcone and various anti-apoptotic proteins, including the mTOR protein. Chalcone was identified as 2',4-dihydroxy-4',6'-dimethoxy-chalcone (DDC). This compound demonstrated a selective inhibition of BC cell proliferation and triggered autophagy and intrinsic apoptosis. It induced cell cycle arrest in the G0/G1 phase and altered mitochondrial outer membrane potential (∆ψm). The study detected the activation of autophagic LC3-II and mitochondrial pro-apoptotic proteins in both BC cell lines. The regulation of Bcl-XL and Bcl-2 proteins varied according to the BC subtype, yet they showed promising molecular interactions with DDC. Among the examined pro-survival proteins, mTOR and Mcl-1 exhibited the most favorable binding energies and were downregulated in BC cell lines. Further research is needed to fully understand the molecular dynamics involved in the activation and interaction of autophagy and apoptosis pathways in cancer cells in response to potential anticancer agents, like the hydroxy-methylated flavonoids from .
乳腺癌（BC）是女性中最常见的癌症之一。有效的治疗需要根据癌症的基因组成进行精确调整，以提高疗效。众多研究集中在天然化合物及其抗乳腺癌特性上，以改善现有的治疗选择。（克拉特）R.M. 金和H. 罗布（. 是生物活性羟基甲基化黄酮类化合物的一个显著来源。然而，这些黄酮类化合物，特别是植物花序中存在的那些化合物的具体抗BC机制仍部分不明。本研究重点评估从花序中提取的一种查尔酮衍生物在腔面A型和三阴性BC细胞中同时激活调节性自噬和内源性凋亡的潜力。我们使用紫外（UV）和核磁共振（NMR）光谱法确定了查尔酮的化学成分。使用MTT法评估其对BC细胞系的选择性细胞毒性。采用流式细胞术和蛋白质印迹分析来检测调控自噬和内源性凋亡途径的蛋白质的调节情况。此外，进行了计算机模拟以预测查尔酮与各种抗凋亡蛋白，包括mTOR蛋白之间的相互作用。查尔酮被鉴定为2',4 - 二羟基 - 4',6'-二甲氧基查尔酮（DDC）。该化合物表现出对BC细胞增殖的选择性抑制，并触发自噬和内源性凋亡。它诱导细胞周期停滞在G0/G1期并改变线粒体膜电位（∆ψm）。该研究在两种BC细胞系中均检测到自噬性LC3-II和线粒体促凋亡蛋白的激活。Bcl-XL和Bcl-2蛋白的调节因BC亚型而异，但它们与DDC显示出有前景的分子相互作用。在所检测的促生存蛋白中，mTOR和Mcl-1表现出最有利的结合能，并在BC细胞系中下调。需要进一步研究以充分了解癌细胞中自噬和凋亡途径在响应潜在抗癌剂（如来自. 的羟基甲基化黄酮类化合物）时的激活和相互作用所涉及的分子动力学。
