Department of Applied Medical Chemistry, Medical Research Institute, Alexandria University, Alexandria, Egypt.
Department of Chemistry, Faculty of Science, Damietta University, Damietta, Egypt.
J Cell Biochem. 2019 Mar;120(3):4278-4290. doi: 10.1002/jcb.27713. Epub 2018 Oct 26.
The treatment of triple-negative breast cancer (TNBC) remains a major challenge. The present study aimed to throw more light on the role of copper (I)-nicotinate complex (CNC) as an antitumor as well as a proapoptotic agent. In this study, the HCC-1806 cell line was used as a model for TNBC. Cell cycle, apoptosis assay, and programmed cell death protein-1 were investigated by flowcytometry. Besides, the comet assay was performed using a fluorescence microscope. The enzyme-linked immunosorbent assay technique was used for the detection of phospho-Chk1 at ser 317 and caspase-3. Moreover, the gene expression of survivin was identified by real-time polymerase chain reaction. Finally, superoxide dismutase (SOD) was calorimetrically assayed. The viability of HCC-1806 cells treated with CNC was decreased in a dose-dependent manner. The tendency for apoptotic machinery was observed through the increase in the sub G0 peak, the percentage of early and late apoptotic phases, and the elevation in caspase-3 levels associated with a downregulation of the survivin gene expression. The antioxidant property of the complex, reflected by elevated SOD activity, may contribute to mediate the cell death pathways. Low concentrations of CNC were found to favor the apoptotis-mediated mechanism. However, one cannot neglect the abundance of cell necrosis-mediated death of cells via CNC, especially at higher concentrations.
三阴性乳腺癌（TNBC）的治疗仍然是一个主要挑战。本研究旨在更深入地探讨铜（I）-烟酸络合物（CNC）作为抗肿瘤和促凋亡剂的作用。在这项研究中，使用 HCC-1806 细胞系作为 TNBC 的模型。通过流式细胞术研究细胞周期、凋亡测定和程序性细胞死亡蛋白-1。此外，使用荧光显微镜进行彗星试验。酶联免疫吸附测定技术用于检测丝氨酸 317 磷酸化 Chk1 和 caspase-3。此外，通过实时聚合酶链反应鉴定 survivin 基因的表达。最后，通过比色法测定超氧化物歧化酶（SOD）。HCC-1806 细胞经 CNC 处理后的活力呈剂量依赖性下降。通过增加亚 G0 峰、早晚期凋亡阶段的百分比以及 caspase-3 水平的升高，观察到凋亡机制的趋势，同时下调 survivin 基因的表达。该复合物的抗氧化特性，反映在升高的 SOD 活性上，可能有助于介导细胞死亡途径。低浓度的 CNC 被发现有利于凋亡介导的机制。然而，不能忽视 CNC 通过细胞坏死介导的细胞死亡的丰富性，尤其是在更高浓度下。
