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  • Decavanadate and metformin-decavanadate effects in human melanoma cells
    Publication . de Sousa-Coelho, Ana Luísa; Aureliano, Manuel; Fraqueza, Gil; Serrão, Gisela; Gonçalves, João; Sánchez-Lombardo, Irma; Link, Wolfgang; Ferreira, Bibiana
    Decavanadate is a polyoxometalate (POMs) that has shown extensive biological activities, including antidiabetic and anticancer activity. Importantly, vanadium-based compounds as well as antidiabetic biguanide drugs, such as metformin, have shown to exert therapeutic effects in melanoma. A combination of these agents, the metformin-decavanadate complex, was also recognized for its antidiabetic effects and recently described as a better treatment than the monotherapy with metformin enabling lower dosage in rodent models of diabetes. Herein, we compare the effects of decavanadate and metformin-decavanadate on Ca2+-ATPase activity in sarcoplasmic reticulum vesicles from rabbit skeletal muscles and on cell signaling events and viability in human melanoma cells. We show that unlike the decavanadate-mediated non-competitive mechanism, metformin-decavanadate inhibits Ca2+-ATPase by a mixed-type competitive-non-competitive inhibition with an IC50 value about 6 times higher (87 mu M) than the previously described for decavanadate (15 mu M). We also found that both decavanadate and metformin-decavanadate exert antiproliferative effects on melanoma cells at 10 times lower concentrations than monomeric vanadate. Western blot analysis revealed that both, decavanadate and metformin-decavanadate increased phosphorylation of extracellular signal-regulated kinase (ERK) and serine/ threonine protein kinase AKT signaling proteins upon 24 h drug exposure, suggesting that the anti-proliferative activities of these compounds act independent of growth-factor signaling pathways.
  • Inhibition of SERCA and PMCA Ca2+-ATPase activities by polyoxotungstates
    Publication . Aureliano, Manuel; Fraqueza, Gil; Berrocal, Maria; Cordoba-Granados, Juan J.; Gumerova, Nadiia I.; Rompel, Annette; Gutierrez-Merino, Carlos; Mata, Ana M.
    Plasma membrane calcium ATPases (PMCA) and sarco(endo) reticulum calcium ATPases (SERCA) are key proteins in the maintenance of calcium homeostasis. Herein, we compare for the first time the inhibition of SERCA and PMCA calcium pumps by several polyoxotungstates (POTs), namely by Wells-Dawson phospho-tungstate anions [P2W18O62]6-(intact, {P2W18}), [P2W17O61]10-(monolacunary, {P2W17}), [P2W15O56]12-(trilacunary, {P2W15}), [H2P2W12O48]12-(hexalacunary, {P2W12}), [H3P2W15V3O62]6- (trivanadium-substituted, {P2W15V3}) and by Preyssler-type anion [NaP5W30O110]14-({P5W30}). The speciation in the solu-tions of tested POTs was investigated by 31P and 51V NMR spectroscopy. The tested POTs inhibited SERCA Ca2+- ATPase activity, whereby the Preyssler POT showed the strongest effect, with an IC50 value of 0.37 mu M. For {P2W17} and {P2W15V3} higher IC50 values were determined: 0.72 and 0.95 mu M, respectively. The studied POTs showed to be more potent inhibitors of PMCA Ca2+-ATPase activity, with lower IC50 values for {P2W17}, {P5W30} and {P2W15V3}.
  • The Ca2+-ATPase inhibition potential of gold (I, III) compounds
    Publication . Fonseca, Custódia; Fraqueza, Gil; Carabineiro, Sónia A.; Aureliano, Manuel
    The therapeutic applications of gold are well-known for many centuries. The most used gold compounds contain Au(I). Herein, we report, for the first time, the ability of four Au(I) and Au(III) complexes, namely dichloro (2-pyridinecarboxylate) Au(III) (abbreviated as1), chlorotrimethylphosphine Au(I) (2), 1,3-bis(2,6-diisopropylphenyl) imidazole-2-ylidene Au(I) chloride (3), and chlorotriphenylphosphine Au(I) (4), to affect the sarcoplasmic reticulum (SR) Ca2+-ATPase activity. The tested gold compounds strongly inhibit the Ca2+-ATPase activity with different effects, being Au(I) compounds2and4the strongest, with half maximal inhibitory concentration (IC50) values of 0.8 and 0.9 mu M, respectively. For Au(III) compound1and Au(I) compound3, higher IC(50)values are found (4.5 mu M and 16.3 mu M, respectively). The type of enzymatic inhibition is also different, with gold compounds1and2showing a non-competitive inhibition regarding the native substrate MgATP, whereas for Au compounds3and4, a mixed type of inhibition is observed. Our data reveal, for the first time, Au(I) compounds with powerful inhibitory capacity towards SR Ca(2+)ATPase function. These results also show, unprecedently, that Au (III) and Au(I) compounds can act as P-type ATPase inhibitors, unveiling a potential application of these complexes.
  • Repurposing therapeutic drugs complexed to Vanadium in Cancer
    Publication . De Sousa-Coelho, Ana Luísa; Fraqueza, Gil; Aureliano, M.
    Repurposing drugs by uncovering new indications for approved drugs accelerates the process of establishing new treatments and reduces the high costs of drug discovery and development. Metal complexes with clinically approved drugs allow further opportunities in cancer therapy—many vanadium compounds have previously shown antitumor effects, which makes vanadium a suitable metal to complex with therapeutic drugs, potentially improving their efficacy in cancer treatment. In this review, covering the last 25 years of research in the field, we identified non-oncology-approved drugs suitable as ligands to obtain different vanadium complexes. Metformin-decavanadate, vanadium-bisphosphonates, vanadyl(IV) complexes with non-steroidal anti-inflammatory drugs, and cetirizine and imidazole-based oxidovanadium(IV) complexes, each has a parent drug known to have different medicinal properties and therapeutic indications, and all showed potential as novel anticancer treatments. Nevertheless, the precise mechanisms of action for these vanadium compounds against cancer are still not fully understood.
  • Alimentos com história: histórias de alimentos
    Publication . Cruz, Ana Lúcia; Quintas, Célia; Esteves, Eduardo; Fraqueza, Gil; Ratao, Isabel; Aníbal, Jaime; Melo, Jessie; Pereira, Jorge; Jesus, José; Galego, Ludovina; Patarata, L; Vieira, Margarida; A. Nunes, Patrícia; Pires-Cabral, Paula; Cruz, Rui; Matos, T. J. S.; Quintas, Célia; Esteves, Eduardo; Aníbal, Jaime; Cruz, Rui
    A Dieta Mediterrânica é um património histórico ativo que depende da utilização sustentável de recursos, guiando-se pelos ritmos da natureza e pelo respeito pela biodiversidade. O conceito de Dieta Mediterrânica não compreende apenas a alimentação, todavia os aspetos relacionados com os hábitos alimentares, os alimentos e a sua preparação são marcadores da identidade coletiva de um povo. Assim, este modelo cultural é indissociável das técnicas de processamento dos alimentos com vista à sua transformação, conservação e até ao seu armazenamento. É neste contexto que surge o livro Alimentos com História-histórias de alimentos que tem como como objetivo descrever alimentos produzidos tradicionalmente no Algarve e as técnicas de processamento ancestrais utilizadas, possuindo um carácter de divulgação. Cada capítulo inclui um resumo e uma introdução onde se apresenta de uma forma sumária o tema, enquadrado no conhecimento existente. Os capítulos abordam um alimento ou grupos de alimentos e compreendem um enquadramento histórico, o tipo de processamento e o seu diagrama de fabrico, e a caracterização sensorial/nutricional (ou outra). Alguns alimentos tradicionais da cultura alimentar algarvia, muitos deles “esquecidos” ou quase, como as azeitonas de mesa, os queijos de cabra, as sardinhas amarelas, o litão, a muxama, a estupeta, os produtos de salchicharia (linguiça, morcela de arroz), e algumas bebidas destiladas, estão associados à identidade regional e a sua degustação é uma oportunidade de saborear a história do processamento de alimentos e a tradição! Alguns são verdadeiros produtos gourmet! Não devem ser esquecidos! Não podem ser apagados das memórias! Trata-se de um legado cultural imaterial valioso, que evoluiu ao longo dos últimos 9000 anos, mas frágil que deve ser salvaguardado para chegar às gerações vindouras. Simultaneamente constitui uma oportunidade para o setor agroalimentar, restauração e hotelaria, uma vez que inclui processos e produtos diferenciados que caracterizam a história alimentar da região algarvia. Esperamos que este livro possa, não só enaltecer as práticas ancestrais, mas também despertar a curiosidade das novas gerações na sua preservação e disseminação, de forma que não se tornem apenas “histórias” da nossa História.