Browsing by Author "Dias, Catarina"
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- Isololiolide, a carotenoid metabolite isolated from the brown alga Cystoseira tamariscifolia, is cytotoxic and able to induce apoptosis in hepatocarcinoma cells through caspase-3 activation, decreased Bcl-2 levels, increased p53 expression and PARP cleavagePublication . Vizetto-Duarte, C; Custódio, Luísa; Gangadhar, Katkam N.; Lago, João Henrique G.; Dias, Catarina; Matos, Ana Marta; Neng, Nuno; Nogueira, José Manuel Florêncio; Barreira, Luísa; Albericio, Fernando; Rauter, Amelia P.; Varela, JoãoBackground: Brown macroalgae have attracted attention because they display a wide range of biological activities, including antitumoral properties. In this study we isolated isololiolide from Cystoseira tamariscifolia for the first time.Purpose: To examine the therapeutical potential of isololiolide against tumor cell lines.Methods/Study design: The structure of the compound was established and confirmed by 1D and 2D NMR as well as HRMS spectral analysis. The in vitro cytotoxicity was analyzed by colorimetric 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide assay in tumoral as well as in non-tumoral cell lines. Cell cycle arrest and induction of apoptosis were assessed by flow cytometry. Alteration of expression levels in proteins important in the apoptotic cascade was analyzed by western blotting.Results: Isololiolidewas isolated for the first time from the brown macroalga C. tamariscifolia. Isololiolide exhibited significant cytotoxic activity against three human tumoral cell lines, namely hepatocarcinoma HepG2 cells, whereas no cytotoxicity was found in non-malignant MRC-5 and HFF-1 human fibroblasts. Isololiolide completely disrupted the HepG2 normal cell cycle and induced significant apoptosis. Moreover, western blot analysis showed that isololiolide altered the expression of proteins that are important in the apoptotic cascade, increasing PARP cleavage and p53 expression while decreasing procaspase-3 and Bcl-2 levels.Conclusion: Isololiolide isolated from C. tamariscifolia is able to exert a selective cytotoxic activity on hepatocarcinoma HepG2 cells as well as induce apoptosis through the modulation of apoptosis-related proteins. (C) 2016 Elsevier GmbH. All rights reserved.
- Utilização de compostos com atividade antimalárica no controlo de perkinsiose em bivalvesPublication . Cabral, Lília; Dias, Catarina; Leite, Ricardo; Cristiano, Maria De LurdesOutbreaks of protozoan agents such as Perkinsus olseni represent major losses for the shellfish producers, urging the development of measures to contain and decrease these episodes. Antimalarial drugs and selective inhibitors designed to target unique metabolic features of the parasite (metabolisms that are not replicated in the host, such as the folate, and shikimate pathways), have been successfully used in the laboratory to inhibit Perkinsus proliferation. However, due to specificities in Perkinsus species and the surrounding environment, development of drug candidates requires further optimization at the molecular level, to improve pharmacologic properties, as well as development of suitable tests and administration protocols for adequate use. Recent advances and future perspectives on the use endoperoxide-type antimalarials for perkinsosis therapy are presented and discussed.