Avaliação da atividade sinérgica entre compostos naturais puros e o quimoterápico docetaxel em modelos celulares de câncer de próstata

• Ano de defesa: 2020
• Autor(a) principal: Guimarães, Gabriela da Silva
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Uberlândia; Brasil; Programa de Pós-graduação em Genética e Bioquímica
• Palavras-chave em Português: Sinergismo; Câncer de Próstata Resistente a Castração; 4-nerolidilcatecol; Docetaxel; Produtos Naturais; Synergism; Castration-Resistant Prostate Cancer; 4-nerolidylcatechol; Natural Products; CNPQ::CIENCIAS BIOLOGICAS::GENETICA::GENETICA MOLECULAR E DE MICROORGANISMOS; Próstata - Câncer
• Link de acesso: https://repositorio.ufu.br/handle/123456789/31300; http://doi.org/10.14393/ufu.di.2021.5004

Prostate cancer (CaP) is a highly incident tumor in the world, curable when detected in early stages, but it can evolve into a more severe form, which refracts to the androgen deprivation treatment, called castration-resistant CaP (CRPC). For these patients, chemotherapy drugs such as Docetaxel (DOC) are used, which also causes side effects and may not be effective due to the resistance developed by the patients. In this scenario, natural products (PNs) stand out, since these substances are important sources of new antitumor drugs. However, it is also necessary to use combined treatments, since the synergism between drugs allows to increase the therapeutic action, reduce the administered dose, attenuate resistance and combat multiple subpopulations of cells. In the present study, the effect of combinations between PNs 4-nerolidylcatechol (4-NC) and Parthenolide (PTL) and DOC against prostatic strains RWPE-01 (non-tumorigenic), LNCaP (androgen-sensitive tumorigenic) and PC3 (CRPC) using the Chou-Talalay method. For PTL, none of the combinations were shown to be synergistic. The interaction between 4-NC and DOC demonstrated a synergistic effect for CRPC PC3 cells after 48 hours of treatment, being antagonistic for LNCaP. The synergistic combination allowed the reduction of the DOC concentration, with cytotoxicity and apoptosis induction superior to the treatments with the isolated compounds. In addition, when 4-NC was co-administered with DOC, there was a significant increase in the expression of proteins associated with the epithelial phenotype, controlling the epithelial-mesenchymal transition. The findings in the present study suggest that the combination of the natural compound 4-NC combined with reduced doses of the chemotherapeutic DOC may represent a promising strategy for the treatment of CRPC. However, additional studies are needed to prove its efficacy and safety in animal models.