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

• Published in: Molecules (Basel, Switzerland) Vol. 27; no. 20; p. 7097
• Main Authors: 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 Cota, Siqueira, Raoni Pais, Goulart Filho, Luiz Ricardo, Guerra, Wendell, Oliveira Júnior, Robson José de, Araújo, Thaise Gonçalves de
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 20.10.2022; MDPI
• Subjects: Cancer therapies; Carcinogens; cell proliferation; Chemotherapy; Copper; Copper compounds; copper(II) complexes; Cyclin D1; Cytotoxicity; Doxorubicin; Drosophila melanogaster; Drug dosages; Drug resistance; Drugs; Flow cytometry; Fruit flies; Mutation; Neoplasms; Prostate cancer; Recombination; Side effects; Toxicity; Toxicity testing; Tumors
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules27207097

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.