4-Nerolidylcatechol (4-NC) and Docetaxel Synergize in Controlling Androgen- independent Prostate Cancer Cells.

Autor: da Silva Guimarães G; Laboratory of Genetics and Biotechnology, Institute of Biotechnology, Federal University of Uberlandia, Patos de Minas-MG, 387400-128, Brazil.; Laboratorty of Nanobiotecnology Prof. Dr. Luiz Ricardo Goulart Filho, Institute of Biotechnology, Federal University of Uberlandia, Uberlandia-MG, 38400-902, Brazil., Cordeiro AO; Laboratory of Genetics and Biotechnology, Institute of Biotechnology, Federal University of Uberlandia, Patos de Minas-MG, 387400-128, Brazil.; Laboratorty of Nanobiotecnology Prof. Dr. Luiz Ricardo Goulart Filho, Institute of Biotechnology, Federal University of Uberlandia, Uberlandia-MG, 38400-902, Brazil., Gazolla MC; Department of Pharmaceutical Sciences, Faculty of Pharmacy, Federal University of Juiz de Fora, Juiz de Fora-MG, 36036-900, Brazil., Vecchi L; Laboratorty of Nanobiotecnology Prof. Dr. Luiz Ricardo Goulart Filho, Institute of Biotechnology, Federal University of Uberlandia, Uberlandia-MG, 38400-902, Brazil., Pereira Zoia MA; Laboratorty of Nanobiotecnology Prof. Dr. Luiz Ricardo Goulart Filho, Institute of Biotechnology, Federal University of Uberlandia, Uberlandia-MG, 38400-902, Brazil., de Vasconcelos Azevedo FVP; Laboratorty of Nanobiotecnology Prof. Dr. Luiz Ricardo Goulart Filho, Institute of Biotechnology, Federal University of Uberlandia, Uberlandia-MG, 38400-902, Brazil., Moreira Campos I; Department of Pharmaceutical Sciences, Faculty of Pharmacy, Federal University of Juiz de Fora, Juiz de Fora-MG, 36036-900, Brazil., de Souza Costa D; Department of Pharmaceutical Sciences, Faculty of Pharmacy, Federal University of Juiz de Fora, Juiz de Fora-MG, 36036-900, Brazil., Soares Mota ST; Laboratory of Genetics and Biotechnology, Institute of Biotechnology, Federal University of Uberlandia, Patos de Minas-MG, 387400-128, Brazil.; Laboratorty of Nanobiotecnology Prof. Dr. Luiz Ricardo Goulart Filho, Institute of Biotechnology, Federal University of Uberlandia, Uberlandia-MG, 38400-902, Brazil., Alves Ribeiro M; Laboratory of Genetics and Biotechnology, Institute of Biotechnology, Federal University of Uberlandia, Patos de Minas-MG, 387400-128, Brazil., Goulart LR; Laboratorty of Nanobiotecnology Prof. Dr. Luiz Ricardo Goulart Filho, Institute of Biotechnology, Federal University of Uberlandia, Uberlandia-MG, 38400-902, Brazil., da Silva Filho AA; Department of Pharmaceutical Sciences, Faculty of Pharmacy, Federal University of Juiz de Fora, Juiz de Fora-MG, 36036-900, Brazil., Araújo TG; Laboratory of Genetics and Biotechnology, Institute of Biotechnology, Federal University of Uberlandia, Patos de Minas-MG, 387400-128, Brazil.; Laboratorty of Nanobiotecnology Prof. Dr. Luiz Ricardo Goulart Filho, Institute of Biotechnology, Federal University of Uberlandia, Uberlandia-MG, 38400-902, Brazil.
Jazyk: angličtina
Zdroj: Current topics in medicinal chemistry [Curr Top Med Chem] 2023; Vol. 23 (11), pp. 943-955.
DOI: 10.2174/1568026623666230207095253
Abstrakt: Background: Effective cancer treatment still challenges medicine since the strategies employed so far are not sufficiently safe and capable of specifically eliminating tumor cells. Prostate cancer (PCa) is a highly incident malignant neoplasm, and the outcome of patients, especially those with advanced castration-resistant PCa (CRPC), depends directly on the efficacy of the therapeutic agents, such as docetaxel (DOC).
Objectives: This study investigated the synergistic potentiation of 4-nerolidylcatechol (4-NC) with DOC in inhibiting androgen-independent PCa cells.
Methods: The cytotoxic effect of 4-NC was evaluated against non-tumorigenic (RWPE-01) and PCa cell lines (LNCaP and PC-3), and the antiproliferative potential of 4-NC was assessed by flow cytometry and colony formation. The Chou-Talalay method was applied to detect the synergistic effect of 4-NC and DOC, and the mechanism of anticancer activities of this combination was investigated by analyzing players in epithelial-mesenchymal transition (EMT).
Results: 4-NC significantly reduced the viability of PC-3 cells in a dose-dependent manner, decreasing colony formation and proliferation. The combination of 4-NC and DOC was synergistic in the androgen-independent cells and allowed the reduction of DOC concentration, with increased cytotoxicity and induction of apoptosis when compared to compounds alone. Furthermore, when 4- NC was co-administered with DOC, higher expression levels of proteins associated with the epithelial phenotype were observed, controlling EMT in PC-3 cells.
Conclusion: Collectively, these data demonstrated, for the first time, that the combination of 4-NC with reduced doses of DOC could be especially valuable in the suppression of oncogenic mechanisms of androgen-independent PCa cells.
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Databáze: MEDLINE