Autor: |
Bontempo NJS; Instituto de Biotecnologia, Universidade Federal de Uberlândia, Uberlândia 38400-902, Brazil., Paixão DA; Instituto de Química, Universidade Federal de Uberlândia, Uberlandia 38400-089, Brazil., Lima PMAP; Instituto de Biotecnologia, Universidade Federal de Uberlândia, Uberlândia 38400-902, Brazil., Barros DCT; Instituto de Biotecnologia, Universidade Federal de Uberlândia, Uberlândia 38400-902, Brazil., Borges DS; Instituto de Biotecnologia, Universidade Federal de Uberlândia, Uberlândia 38400-902, Brazil., Orsolin PC; Laboratory of Cytogenetic and Mutagenesis, Centro Universitário de Patos de Minas, Patos de Minas 38700-207, Brazil., Martins IC; Instituto de Biotecnologia, Universidade Federal de Uberlândia, Uberlândia 38400-902, Brazil., Machado PHA; Instituto de Biotecnologia, Universidade Federal de Uberlândia, Uberlândia 38400-902, Brazil., Lino RC; Instituto de Biotecnologia, Universidade Federal de Uberlândia, Uberlândia 38400-902, Brazil., Souza TR; Instituto de Biotecnologia, Universidade Federal de Uberlândia, Uberlândia 38400-902, Brazil., Ramos LMS; Instituto de Química, Universidade Federal de Uberlândia, Uberlandia 38400-089, Brazil., Teixeira SC; Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Uberlandia 38405-318, Brazil., Siqueira RP; Instituto de Biotecnologia, Universidade Federal de Uberlândia, Uberlândia 38400-902, Brazil., Goulart Filho LR; Instituto de Biotecnologia, Universidade Federal de Uberlândia, Uberlândia 38400-902, Brazil., Guerra W; Instituto de Química, Universidade Federal de Uberlândia, Uberlandia 38400-089, Brazil., Oliveira Júnior RJ; Instituto de Biotecnologia, Universidade Federal de Uberlândia, Uberlândia 38400-902, Brazil., Araújo TG; Instituto de Biotecnologia, Universidade Federal de Uberlândia, Uberlândia 38400-902, Brazil. |
Abstrakt: |
Prostate Cancer (PCa) is the second leading cause of cancer-related deaths among men worldwide. The treatment of advanced cases is based on chemotherapy, which lacks specificity and efficacy, due to severe side effects and resistance to the traditional drugs. Copper complexes have shown antitumoral efficacy and low toxicity, being considered a promising class of metal-based drugs for the treatment of malignant neoplasms. Thus, the present study aimed to evaluate the cellular effects of a copper(II) complex with 4-fluorophenoxyacetic acid hydrazide and 1,10-phenanthroline ( 1 ) on PCa cell lines, as well as the mutagenic/recombinogenic and anticarcinogenic potential of 1 in Drosophila melanogaster. PNT-2 (non-tumorigenic), LNCaP (hormone-responsive PCa) and PC-3 (androgen-independent PCa) cells were cultured, and cytotoxicity was assessed using the MTT assay. The expression levels of the proliferation markers Ki-67 and Cyclin D1 were analyzed by flow cytometry. Furthermore, the Somatic Mutation and Recombination Test (SMART) and the Epithelial Tumor Test (ETT) were performed. Complex 1 was selective to LNCaP cells, significantly reducing Ki-67 and Cyclin D1 expression levels. Sub-toxic concentrations of complex 1 were defined by the toxicity test in D. melanogaster , and no mutagenic/recombinogenic/carcinogenic effects were observed. Anticarcinogenic potential was observed in D. melanogaster , suggesting modulating activity of the complex 1 against Doxorubicin, a drug used as control by its carcinogenic properties. Therefore, complex 1 is a possible starting point for the development of new antitumor agents for the treatment of PCa. |