Percorrer por autor "Botana, Luis M."
A mostrar 1 - 4 de 4
Resultados por página
Opções de ordenação
- Bromoditerpenes from the red seaweed Sphaerococcus coronopifolius as potential cytotoxic agents and proteasome inhibitors and related mechanisms of actionPublication . Alves, Celso; Silva, Joana; Pintéus, Susete; Guedes, Romina A.; Guedes, Rita C.; Alvariño, Rebeca; Freitas, Rafaela; Goettert, Márcia I.; Gaspar, Helena; Alfonso, Amparo; Alpoím, Maria C.; Botana, Luis M.; Pedrosa, RuiSeaweeds are a great source of compounds with cytotoxic properties with the potential to be used as anticancer agents. This study evaluated the cytotoxic and proteasome inhibitory activities of 12R-hydroxy-bromosphaerol, 12S-hydroxy-bromosphaerol, and bromosphaerol isolated from Sphaerococcus coronopifolius. The cytotoxicity was evaluated on malignant cell lines (A549, CACO-2, HCT-15, MCF-7, NCI-H226, PC-3, SH-SY5Y, and SK-MEL-28) using the MTT and LDH assays. The ability of compounds to stimulate the production of hydrogen peroxide (H2O2) and to induce mitochondrial dysfunction, the externalization of phosphatidylserine, Caspase-9 activity, and changes in nuclear morphology was also studied on MCF-7 cells. The ability to induce DNA damage was also studied on L929 fibroblasts. The proteasome inhibitory activity was estimated through molecular docking studies. The compounds exhibited IC50 values between 15.35 and 53.34 μM. 12Rhydroxy-bromosphaerol and 12S-hydroxy-bromosphaerol increased the H2O2 levels on MCF-7 cells, and bromosphaerol induced DNA damage on fibroblasts. All compounds promoted a depolarization of mitochondrial membrane potential, Caspase-9 activity, and nuclear condensation and fragmentation. The compounds have been shown to interact with the chymotrypsin-like catalytic site through molecular docking studies; however, only 12S-hydroxy-bromosphaerol evidenced interaction with ALA20 and SER169, key residues of the proteasome catalytic mechanism. Further studies should be outlined to deeply characterize and understand the potential of those bromoditerpenes for anticancer therapeutics.
- Marine invasive macroalgae: Turning a real threat into a major opportunity - the biotechnological potential of Sargassum muticum and Asparagopsis armataPublication . Pinteus, Susete; Lemos, Marco F.L.; Alves, Celso; Neugebauer, Agnieszka; Silva, Joana; Thomas, Olivier P.; Botana, Luis M.; Gaspar, Helena; Pedrosa, RuiMarine invasive species are widely recognized as one of the worst threats to marine ecosystems integrity, un-balancing native communities, which may lead to paramount ecological and economic impacts. Within invasiveseaweeds, Sargassum muticum and Asparagopsis armata are recognized as successful invaders in Europe andAmerica. Despite several attempts to control the spread of marine invaders, until now, all have proven to beelusive, and therefore, alternative strategies should be embraced.Worldwide, seaweeds have been increasingly explored due to their ability to produce bioactive compounds.However, one of the main problems associated with the production/extraction of these bioactive compounds fornew products development, is the source availability and the potential negative environmental consequences ofthis exploitation.Within this framework, the use of invasive species to obtain natural bioactive compounds presents us with atwo-folded opportunity - high availability of the biological material for the extraction of unique bioactivecompounds for new products development, and through specimen collection, mitigating negative effects causedby alien species, contributing for ecosystem integrity and sustainability.Over the last decades, the brown seaweed S. muticum and the red A. armata have been studied all over theworld for their capacity to produce bioactive compounds, with main results pointing towards their high potentialas producers of antioxidant, antifouling, antimicrobial, and antitumor compounds.The present review summarizes the biotechnological potential of S. muticum and A. armata as producers ofbioactive compounds, while addressing the potential use of global threats as important blue growth pawns.
- Sphaerococcus coronopifolius bromoterpenes as potential cancer stem cell-targeting agentsPublication . Alves, Celso; Serrano, Eurico; Silva, Joana; Rodrigues, Carlos; Pinteus, Susete; Gaspar, Helena; Botana, Luis M.; Alpoim, Maria C.; Pedrosa, RuiCancer is one of the major threats to human health and, due to distinct factors, it is expected that its incidence will increase in the next decades leading to an urgent need of new anticancer drugs development. Ongoing experimental and clinical observations propose that cancer cells with stem-like properties (CSCs) are involved on the development of lung cancer chemoresistance. As tumour growth and metastasis can be controlled by tumourassociated stromal cells, the main goal of this study was to access the antitumor potential of five bromoterpenes isolated from Sphaerococcus coronopifolius red alga to target CSCs originated in a co-culture system of fibroblast and lung malignant cells. Cytotoxicity of compounds (10–500 μM; 72 h) was evaluated on monocultures of several malignant and non-malignant cells lines (HBF, BEAS-2B, RenG2, SC-DRenG2) and the effects estimated by MTT assay. Co-cultures of non-malignant human bronchial fibroblasts (HBF) and malignant human bronchial epithelial cells (RenG2) were implemented and the compounds ability to selectively kill CSCs was evaluated by sphere forming assay. The interleucine-6 (IL-6) levels were also determined as cytokine is crucial for CSCs. Regarding the monocultures results bromosphaerol selectively eliminated the malignant cells. Both 12S-hydroxy-bromosphaerol and 12R-hydroxy-bromosphaerol steroisomers were cytotoxic towards non-malignant bronchial BEAS-2B cell line, IC50 of 4.29 and 4.30 μM respectively. However, none of the steroisomers induced damage in the HBFs. As to the co-cultures, 12R-hydroxy-bromosphaerol revealed the highest cytotoxicity and ability to abrogate the malignant stem cells; however its effects were IL-6 independent. The results presented here are the first evidence of the potential of these bromoterpenes to abrogate CSCs opening new research opportunities. The 12R-hydroxy-bromosphaerol revealed to be the most promising compound to be test in more complex living models.
- Sustainable production of biologically active molecules of marine based originPublication . Murray, Patrick M.; Moane, Siobhan; Collins, Catherine; Beletskaya, Tanya; Thomas, Olivier P.; Duarte, Alysson W.F.; Nobre, Fernando S.; Owoyemi, Ifeloju O.; Pagnocca, Fernando C.; Sette, L.D.; McHugh, Edward; Causse, Eric; Pérez-López, Paula; Feijoo, Gumersindo; Moreira, Ma.T.; Rubiolo, Juan; Leirós, Marta; Botana, Luis M.; Pinteus, Susete; Alves, Celso; Horta, André; Pedrosa, Rui; Jeffryes, Clayton; Agathos, Spiros N.; Allewaert, Celine; Verween, Annick; Vyverman, Wim; Laptev, Ivan; Sineoky, Sergei; Bisio, Angela; Manconi, Renata; Ledda, Fabio; Marchi, Mario; Pronzato, Roberto; Walsh, Daniel J.The marine environment offers both economic and scientific potential which are relatively untapped from a biotechnological point of view. These environments whilst harsh are ironically fragile and dependent on a harmonious life form balance. Exploitation of natural resources by exhaustive wild harvesting has obvious negative environmental consequences. From a European industry perspective marine organisms are a largely underutilised resource. This is not due to lack of interest but due to a lack of choice the industry faces for cost competitive, sustainable and environmentally conscientious product alternatives. Knowledge of the biotechnological potential of marine organisms together with the development of sustainable systems for their cultivation, processing and utilisation are essential. In 2010, the European Commission recognised this need and funded a collaborative RTD/SME project under the Framework 7-Knowledge Based Bio-Economy (KBBE) Theme 2 Programme 'Sustainable culture of marine microorganisms, algae and/or invertebrates for high value added products'. The scope of that project entitled 'Sustainable Production of Biologically Active Molecules of Marine Based Origin' (BAMMBO) is outlined. Although the Union is a global leader in many technologies, it faces increasing competition from traditional rivals and emerging economies alike and must therefore improve its innovation performance. For this reason innovation is placed at the heart of a European Horizon 2020 Strategy wherein the challenge is to connect economic performance to eco performance. This article provides a synopsis of the research activities of the BAMMBO project as they fit within the wider scope of sustainable environmentally conscientious marine resource exploitation for high-value biomolecules.