Title:4-Nerolidylcatechol (4-NC) and Docetaxel Synergize in Controlling Androgen-
independent Prostate Cancer Cells
Volume: 23
Issue: 11
Author(s): Gabriela da Silva Guimarães, Antonielle Oliveira Cordeiro, Matheus Coutinho Gazolla, Lara Vecchi, Mariana Alves Pereira Zoia, Fernanda Van Petten de Vasconcelos Azevedo, Igor Moreira Campos, Danilo de Souza Costa, Sara Teixeira Soares Mota, Matheus Alves Ribeiro, Luiz Ricardo Goulart, Ademar Alves da Silva Filho and Thaise Gonçalves Araújo*
Affiliation:
- 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
Keywords:
Androgen-independent prostate cancer, Chemotherapy, Epithelial-mesenchymal transition, Natural products, Synergistic, Tumor cell.
Abstract:
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.
