Copper(II) Complex Containing 4-Fluorophenoxyacetic Acid Hydrazide and 1,10-Phenanthroline: A Prostate Cancer Cell-Selective and Low-Toxic Copper(II) Compound

Author:

Bontempo Nayara Júnia de Souza,Paixão Drielly Aparecida,Lima Paula Marynella Alves Pereira,Barros Deysse Carla Tolentino,Borges Dayanne Silva,Orsolin Priscila Capelari,Martins Isabella Castro,Machado Pedro Henrique Alves,Lino Ricardo Campos,Souza Tiago Rodrigues de,Ramos Luana Munique Sousa,Teixeira Samuel CotaORCID,Siqueira Raoni Pais,Goulart Filho Luiz Ricardo,Guerra Wendell,Oliveira Júnior Robson José deORCID,Araújo Thaise Gonçalves deORCID

Abstract

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.

Funder

Fundação de Amparo a Pesquisa de Minas Gerais

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

National Institute of Science and Technology in Theranostics and Nanobiotechnology—INCT—Teranano

Publisher

MDPI AG

Subject

Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science

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