Impact of copper (I) Nicotinate complex on Notch signaling pathway in autophagy-modulated triple-negative breast cancer cell lines

Background : Triple-negative breast cancer (TNBC) is the most aggressive subtype and is distinguished by a short overall survival, chemoresistance, recurrence, and a poor prognosis. Despite the increase in the disease's incidence globally, the development of numerous targeted medications and innovative combination therapies has improved the overall prognosis for individuals with breast cancer. However, this generally encouraging image is tarnished by the development of resistance or the reduced effectiveness of pharmaceutical combinations, even if the basic processes are not understood. For instance, autophagy, a catabolic process intended to recycle damaged cellular components and provide energy, is quickly activated by cancer cells to evade most therapies. Consistent with this theory, there is a rising need for metal substances such as copper complex, which may promote cell death and have a less harmful effect on normal cells. On the other hand, deregulated Notch signaling within the breast tumor and its microenvironment is linked to poor clinical outcomes in the treatment of resistant breast cancer. Objectives : In autophagy-modulated TNBC cell lines, the current study aimed to clarify the possible significance of copper (I) nicotinate complex (CNC) as a targeted therapy for the Notch signaling pathway and evaluated any potential communication between the autophagic process and the Notch signaling pathway. Method : Two distinct TNBC cell lines, HCC1806 and MDA-MB231 cells, were used. To assess the autophagy process, Torin1 was used to stimulate autophagy, while chloroquine was used to inhibit it. The MTT assay was used to determine the cytotoxicity of CNC and the reference treatment, doxorubicin. The indirect antibody labeling of microtubule-associated protein light chain 3 (LC3) was measured using flow cytometry. The Notch signaling pathway-related gene expressions were determined using real-time PCR technique. Results and conclusion : Treatment of TNBC cells with the CNC-modulated Notch signaling pathway significantly differed depending on the type of cell line and CNC concentration used. In conclusion, given CNCs’ concentration and use with Doxo, it may be a viable targeted anticancer treatment for TNBC due to its ability to inhibit Notch signaling in autophagy-modulated TNBC.