الفهرس 
Introduction and Aim of the WorkOnly 14 pages are availabe for public view
 |  | from | 167 |  |  |
| | | from | 167 | | |
Abstract
Triple-negative breast cancer (TNBC) is a diverse subtype of cancer that is frequently described by aggressiveness and represents 12–20% of all breast cancers. Doxorubicin is regarded as the most single therapeutic active agent available for TNBC treatment. However, doxorubicin efficacy is limited due to dose dependent risk of cardiac associated side ef¬fects. Moreover, the resistance to doxorubicin induced apoptotic cell death (type I cell death), directed attention towards other alternative pathways of cell death. On the other hand, current interest in copper complexes e.g., Copper (I)-nicotinate complex (CNC) is stemming from their potential use as antimicrobial, antiviral, anti-inflammatory, antitumor agents. Meanwhile, the most recurrent cell death mechanism elicited by copper agents is apoptosis, the elucidation of more biological targets involved in the anti-proliferative activity of copper (I)-complexes could provide new therapeutic options. Recently, the status of autophagy in cancer therapy has also been given increasing attention. In addition, the double-edged sword function of autophagy, as both a tumor suppressor and a protector of cancer cell survival, is more likely to influence anticancer treatment efficacy in opposing ways Accordingly, the present study was designed to investigate the potential antitumor role of Copper (I)–nicotinate complex (CNC) on TNBC cell line and to provide new insights for understanding the role of autophagy modulation on CNC and Doxorubicin as a potential target for development of effective therapeutic strategies for treatment.
The present study may be among the first studies to demonstrate that CNC may possess a potential down-regulation effect on autophagy in TNBC. This effect was evident by treating TNBC cells with CNC either alone or in combination with autophagy inducer, Torin 1, or autophagy inhibitor, CQ. Considering that down-regulation of autophagy has been described as potential adjunctive strategy for enhancing the clinical outcomes of chemotherapy, therefore, the data of present study may lead to the suggestion that CNC, as an autophagy inhibitor and pro-apoptotic agent, could be a promising anti-cancer agent either alone or in combination with chemotherapeutic drugs. Moreover, modulating doxorubicin -induced autophagy could dictate the interplay between autophagy and other cell death pathways lead to lower dose usage and the enhancement of activity. Thus, this study provides many therapeutic options to overcome the aggressiveness of TNBC through modulation of autophagy either by induction or inhibition in combination with CNC or Dox towards the increase of therapeutic effectiveness.