Antitumor Activity of Copper (I)–Nicotinate Complex and Autophagy Modulation in HCC1806 Breast Cancer Cells

Title:Antitumor Activity of Copper (I)–Nicotinate Complex and Autophagy Modulation in HCC1806 Breast Cancer Cells

Volume: 17 Issue: 11

Author(s): Mohamed A. Abdel-Mohsen*, Camelia A. Abdel Malak, Morsy A. Abou Yossef and Eman S. El-Shafey

Affiliation:

• Applied Medical Chemistry Department, Medical Research Institute, Alexandria University, Alexandria,Egypt

Keywords: Primary squamous cell carcinoma, copper (I) nicotinate complex, autophagy, LC3, NBR1 gene, chloroquine, torin1.

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.

Method: 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.

Conclusion: 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.

Cite this article as:

Abdel-Mohsen A. Mohamed*, Abdel Malak A. Camelia , Abou Yossef A. Morsy and El-Shafey S. Eman, Antitumor Activity of Copper (I)–Nicotinate Complex and Autophagy Modulation in HCC1806 Breast Cancer Cells, Anti-Cancer Agents in Medicinal Chemistry 2017; 17 (11) . https://dx.doi.org/10.2174/1871520617666170327144122