Applied Medical Chemistry Department, Medical Research Institute, Alexandria University, Alexandria, Egypt.
Chemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt.
Sci Rep. 2024 Jan 30;14(1):2522. doi: 10.1038/s41598-024-52952-1.
Triple negative breast cancer (TNBC) is a subtype of breast cancer which is characterized by its aggressiveness, poor and short overall survival. In this concept, there is a growing demand for metal-based compounds in TNBC therapy as copper complex that have a less toxic effect on normal cells and could stimulate apoptotic cell death. Additionally, Notch1 signaling pathway has received great attention as one of the most important potential targets for developing a novel therapeutic strategy. The present study is an attempt to assess the promising chemotherapeutic activities of copper(I) nicotinate (CNC) through its impact on the expression of downstream genes of Notch1 signaling pathway and the cell fate of TNBC. The co-treatment of TNBC cells with doxorubicin (Doxo) and CNC was also investigated. To approach the objective of the present study, TNBC cell lines; HCC1806 and MDAMB231, were utilized. MTT assay was used to determine the IC values of CNC and Doxo. After treatment, microtubule-associated protein light chain3 (LC3) were determined by flow cytometry. Additionally, qRT-PCR technique was used to detect the changes in genes levels that are involved Notch1 signaling pathway. Moreover, autophagosomes were monitored and imaged by Transmission electron microscopy. Treatment of TNBC cells with CNC modulated Notch1 signaling pathway in different manners with respect to the type of cells and the applied dose of CNC. The observed effects of CNC may reflect the possible anti-cancer activities of CNC in both types of TNBC. However, cell type and CNC dose should be considered.
三阴性乳腺癌（TNBC）是一种侵袭性强、总体预后不良且较短的乳腺癌亚型。在这种情况下，人们对 TNBC 治疗中基于金属的化合物的需求越来越大，例如铜配合物，它对正常细胞的毒性较小，并能刺激细胞凋亡。此外，Notch1 信号通路已受到极大关注，成为开发新治疗策略的最重要潜在靶点之一。本研究试图通过评估铜（I）烟酸盐（CNC）对 Notch1 信号通路下游基因表达和 TNBC 细胞命运的影响，来评估其有前途的化疗活性。还研究了 TNBC 细胞与多柔比星（Doxo）和 CNC 的联合治疗。为了达到本研究的目的，使用了 TNBC 细胞系 HCC1806 和 MDAMB231。MTT 测定法用于确定 CNC 和 Doxo 的 IC 值。处理后，通过流式细胞术测定微管相关蛋白轻链 3（LC3）。此外，还使用 qRT-PCR 技术检测参与 Notch1 信号通路的基因水平的变化。此外，通过透射电子显微镜监测和成像自噬体。CNC 处理 TNBC 细胞在不同细胞类型和 CNC 剂量下以不同方式调节 Notch1 信号通路。观察到的 CNC 效应可能反映了 CNC 在两种 TNBC 中的潜在抗癌活性。然而，应考虑细胞类型和 CNC 剂量。
