Citotoxicidade de complexos de Paládio(II) para as linhagens MCF-7 e MDA-MB-435 de adenocarcinoma mamário humano

Abstract

Breast cancer is the prevalent cancer type among women and comprises a heterogeneous group of tumors with different prognoses and responses to treatment, including estrogen receptor positive tumors (ER+), those with overexpression of the receptor to the human epidermal growth factor 2 (HER2+) and triple-negatives. Cisplatin is a chemotherapeutic agent used in clinical practice for the treatment of various tumor types, however, the adverse effects of this compound, limit its use. Thus, the search for new compounds with antitumor activity is important to increase the efficiency of breast cancer treatment. This is the case of palladium(II) complexes. The present study evaluated the cytotoxic activity of the ligand (C1) and palladium(II) complexes(C2-C7), derived from the ligand, to the cell lines MCF-7, breast tumor ER+ and MDA-MB-435, triple-negative breast tumor. The cells were cultured in RPMI medium containing 20% fetal bovine serum and antibiotics, and maintained at 37 oC in humidified atmosphere, with 5% CO2. The following tests were carried out: sulforhodamine (B) for the evaluation of cell viability, clonogenic, migration and adhesion assays, morphological and morphometric studies, genomic DNA fragmentation analysis and plasmidial DNA binding test. The results showed that there was a reduction of cell viability after treatment with palladium(II) complexes and these inhibited completely the cell survival in the clonogenic assay. The treatment induced cell morphological alterations and cell death. Thus the palladium(II) complexes can be considered antitumor compounds. In addition, the complexes inhibited migration and adhesion of the cells to the extracellular matrix, which indicates antimetastatic activity. The complexes showed plasmidial DNA binding capacity and induced break of both plasmidial and genomic DNA, with DNA ladder pattern formation, indicating apoptosis. Thus, the complexes analyzed showed antitumor and antimetastatic activities, can be considered tumor suppressors and their mechanism of action includes the induction of apoptosis. The results of this work indicated that the complexes C5 and C7 were active in all tests, both for MCF-7 and MDA-MB-435 being good candidates for the development of new drugs for the treatment of breast cancer.