title: Antitumor Activity of Copper (I)-Nicotinate Complex and Autophagy Modulation in HCC1806 Breast Cancer Cells.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Applied Medical Chemistry Department, Medical Research Institute, Alexandria University, Alexandria, Egypt.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Abdel-Mohsen
authors.affiliation: Chemistry Department, Faculty of Science, Damietta University, Damietta, Egypt.
authors.forename: Camelia A
authors.initials: CA
authors.lastname: Abdel Malak
authors.affiliation: Chemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt.
authors.forename: Morsy A
authors.initials: MA
authors.lastname: Abou Yossef
authors.affiliation: Chemistry Department, Faculty of Science, Damietta University, Damietta, Egypt.
authors.forename: Eman S
authors.initials: ES
authors.lastname: El-Shafey
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D009525:Niacin / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D009525:Niacin; D003300:Copper
keywords: LC3; NBR1 gene; Primary squamous cell carcinoma; autophagy; chloroquine; copper (I) nicotinate complex; torin1.