Extratos e substâncias naturais promissores para o tratamento do câncer de próstata

Abstract

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 depends directly on the treatment adopted, especially on the efficacy of the chemotherapeutic agents. In this context, the search for active natural products with antineoplastic action is promising. In the present study, is reported the cytotoxic effect of different plant extracts from Brazilian savanna and of the substance 4-nerolidylcatechol (4-NC) against prostate tumor cells. In addition, 4-NC was evaluated for its ability to suppress different mechanisms associated with CaP. Three prostate cell lines were cultured: RWPE-01 (non-tumorigenic), LNCaP (tumorigenic sensitive to androgen) and PC3 (tumorigenic resistant to castration). They were individually treated with hexanic, chloroformic and hydromethanolic extracts from 10 plant species and the cytotoxicity evaluated by the MTT method. The hexanic extract of Pothomorphe umbellata was promising by decreasing the viability of the tumor cell lines.The substance obtained from this hexanic extract of P. umbellata, 4-NC, showed selective cytotoxicity against PCa lineages, especially on PC3, inducing apoptosis, altering mitochondrial membrane potential and reducing proliferation and invasion. Finally, analysis of the expression of 84 genes associated with different oncogenic pathways demonstrated that 4-NC modulated apoptosis, cell cycle, epithelial-mesenchymal Transition (EMT), angiogenesis and hypoxia in PC3 cells. Our findings elucidated the antitumor activity of 4-NC against PCa, which was promising especially in the suppression of oncogenic mechanisms of the castration-resistant model. Further studies are needed to better describe their behavior by validating 4-NC as a new alternative for the treatment of advanced CaP or as a prototype for the development of new antitumor drugs.