Finding new molecular targets of two copper(II)-hydrazones complexes on triple negative breast cancer cells using Mass Spectrometry-based Quantitative Proteomics.

BALSA, L.M.; RODRIGUEZ M.R.; FERRARESI V; PARAJÓN-COSTA B.S; GONZALEZ BARO AG; LEON I.E

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

MOLECULAR DIVERSITY PRESERVATION INTERNATIONAL-MDPI

Lugar: Basel; Año: 2023

1422-0067

Breast cancer is the most common cancer in women, with a high incidence estimated to reach 2.3 million by 2030. Triple Negative Breast Cancer is the greatest invasive class of breast cancer with a poor prognosis, due to side effects exerted by chemotherapy used and low effectivity of novel treatments. In this sense, copper compounds have shown to be potentially effective as antitumor agents, attracting increasing interest as alternatives to usually employed platinum derived drugs. Therefore, the aim of this work is to identify differentially expressed proteins in MDA-MB-231 cells exposed to two copper(II)-hydrazones complexes using label-free quantitative proteomics and functional bioinformatics strategies to identify the molecular mechanisms through which these copper complexes exert their antitumoral effect in TNBC cells. Both copper complexes increased proteins involved in ER stress and UPR, as well as the down-regulation of proteins related to DNA replication and repair. One of the most relevant anticancer mechanisms of action found for CuHL1 and CuHL2 was the down-regulation of GOF-mutant p53. Moreover, we found a novel and in-teresting effect for a copper metallodrug, the down-regulation of proteins related to lipid synthesis and metabolism that could lead to a beneficial decrease in lipid levels.