ECE2017 Eposter Presentations: Interdisciplinary Endocrinology Nuclear receptors and Signal transduction (7 abstracts)
Introduction: Prostate cancer is a public health problem worldwide. The cure is unlikely and therapeutic alternatives are limited. The Brazilian biodiversity represents a huge source of potential discovery of new drugs derived from plants. We therefore aimed to conduct a biomonitoring chemical study of plant extracts from Pouteria sp. previously shown to be cytotoxic in androgen-sensitive (LNCaP) and androgen-resistant (PC3) human prostate cancer cell lines.
Methods: The crude ethanolic extract of Pouteria caimito leaves and hexanic extract of Pouteria ramiflora were tested in PC3 and LNCap human prostate adenocarcinoma cells. The crude extract of P. ramiflora branches and stem was then pre-fractionated through sintered funnel. The pre-fraction hexane: ethyl acetate 1:1 was fractionated by column chromatography into 649 fractions, grouped according to the profile in thin layer chromatography into 49 samples. Among those, four samples were selected for Nuclear Magnetic Resonance (NMR) spectroscopy, based on their abundance and cytotoxicity biomonitored by MTT.
Results: The ethanolic extract of P. caimito showed a dose-dependent cytotoxic effect in PC3 cells (>50%), with a statistically significant inhibitory effect on the cell cycle. The hexanic extract of P. ramiflora showed a dose-dependent cytotoxic effect in LNCaP, with a high selectivity index (5.5 after 48 h of treatment), as compared to a non-cancerous human cell line (HaCat). Among the 49 samples obtained from this extract, fraction 8 was purified and the compound epi-friedelanol was isolated, whose bioactivity is under evaluation in prostate cancer cell lines.
Conclusion: Our biomonitored analysis of Pouteria sp. extracts has provided the purification of a number of cytotoxic fractions. Among those, a triterpenic bioactive compound (epi-friedelanol) was identified by RMN spectroscopy, and deserve further studies regarding its specific cytotoxicity. Triterpens have been shown to exert cytotoxic effects on different types of cancer at low activity towards normal cells, including prostate cancer.
20 May 2017 - 23 May 2017