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.