Abdel-Mohsen Mohamed A, Abdel Malak Camelia A, Abou Yossef Morsy A, El-Shafey Eman S
Applied Medical Chemistry Department, Medical Research Institute, Alexandria University, Alexandria, Egypt.
Chemistry Department, Faculty of Science, Damietta University, Damietta, Egypt.
Anticancer Agents Med Chem. 2017 Nov 24;17(11):1526-1536. doi: 10.2174/1871520617666170327144122.
Squamous cell cancer is a heterogeneous aggressive disease, therefore, its treatment is challenging. Increased attention has been paid to metal complexes as anticancer drugs. However, new insights towards autophagy have been recognized due to its role in tumor cell death or survival.
To clarify the antitumor activity of copper (I) nicotinate complex (CNC) as new therapeutic agent and understand the role of autophagy modulation as a prospective target for the advancement of efficient therapeutic agent for treatment.
Viability of MDA-MB-231 and HCC1806 cells and IC50 values of CNC for both cell lines were assessed by MTT assay. Also, the viability and IC50 values of Torin1 and Chloroquine (CQ) were assessed only in HCC1806 cells by MTT assay. The level of microtubule-associated protein 1 light chain 3 (LC3) was assessed by ELISA. Real time PCR was used to detect the changes in NBR1 gene expression. Cell cycle distribution and quantitative detection of acid vesicular organelles (AVOs) were determined by flow cytometry. Fluorescence microscope was used for qualitative detection of AVOs. Modulation of autophagy was carried out by Torin1 as inducer and CQ as inhibitor.
CNC restrained the growth, in a dose-dependent manner, and induced cell death in human HCC1806 cell line. In addition, the CNC treated cells displayed inhibition of autophagy, as indicated by reduction of AVOs, decrease in LC3 protein level and up regulation of NBR1 gene expression.
CNC, as an autophagy inhibitor and pro-apoptotic agent, could be a promising anti-cancer agent either alone or in combination with other therapeutic drugs.
鳞状细胞癌是一种异质性侵袭性疾病，因此其治疗具有挑战性。金属配合物作为抗癌药物受到了越来越多的关注。然而，由于自噬在肿瘤细胞死亡或存活中的作用，人们对其有了新的认识。
阐明烟酸铜（I）配合物（CNC）作为新型治疗剂的抗肿瘤活性，并了解自噬调节作为开发高效治疗剂的潜在靶点的作用。
通过MTT法评估MDA-MB-231和HCC1806细胞的活力以及CNC对这两种细胞系的IC50值。此外，仅通过MTT法在HCC1806细胞中评估托林1和氯喹（CQ）的活力及IC50值。通过酶联免疫吸附测定法评估微管相关蛋白1轻链3（LC3）的水平。采用实时聚合酶链反应检测NBR1基因表达的变化。通过流式细胞术确定细胞周期分布和酸性囊泡细胞器（AVO）的定量检测。使用荧光显微镜对AVO进行定性检测。以托林1作为诱导剂、CQ作为抑制剂进行自噬调节。
CNC以剂量依赖性方式抑制人HCC1806细胞系的生长并诱导细胞死亡。此外，经CNC处理的细胞显示出自噬抑制，表现为AVO减少、LC3蛋白水平降低以及NBR1基因表达上调。
CNC作为一种自噬抑制剂和促凋亡剂，单独或与其他治疗药物联合使用可能是一种有前景的抗癌药物。
