Percorrer por autor "Costa, Pedro M."
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- Characterization of antiproliferative potential and biological targets of a copper compound containing 4′-phenyl terpyridinePublication . Mendo, Ana Soraia; Figueiredo, Sara; Roma-Rodrigues, Catarina; Videira, Paula A.; Ma, Zhen; Diniz, Mário; Larguinho, Miguel; Costa, Pedro M.; Lima, João C.; Pombeiro, Armando J. L.; Baptista, Pedro V.; Fernandes, Alexandra R.Several copper complexes have been assessed as anti-tumor agents against cancer cells. In this work, a copper compound [Cu(H2O){OS(CH3)2}L](NO3)2 incorporating the ligand 4′-phenyl-terpyridine antiproliferative activity against human colorectal, hepatocellular carcinomas and breast adenocarcinoma cell lines was determined, demonstrating high cytotoxicity. The compound is able to induce apoptosis and a slight delay in cancer cell cycle progression, probably by its interaction with DNA and induction of double-strand pDNA cleavage, which is enhanced by oxidative mechanisms. Moreover, proteomic studies indicate that the compound induces alterations in proteins involved in cytoskeleton maintenance, cell cycle progression and apoptosis, corroborating its antiproliferative potential.
- Co-exposure to environmental carcinogens in vivo induces neoplasia-related hallmarks in low genotoxicity events, even after removal of insultPublication . Martins, Marta; Silva, Ana; Costa, Maria H.; Miguel, Célia; Costa, Pedro M.Addressing the risk of mixed carcinogens in vivo under environmentally-realistic scenarios is still a challenge. Searching for adequate biomarkers of exposure requires understanding molecular pathways and their connection with neoplasia-related benchmark pathologies. Subjecting the zebrafish model to realistic concentrations of two genotoxicants and carcinogens, cadmium and benzo[a]pyrene, isolated and combined, yielded low levels of DNA damage. Altogether, the organisms' mechanisms of DNA repair, oxidative stress and phases I and II were not overwhelmed after two weeks of treatment. Still, transcriptional responses related to detoxification (epoxide hydrolase and UDP-glucuronosyltransferase) were higher in animals subjected to the combination treatment, inclusively following depuration. Nonetheless, inflammation and formation of hyperplasic foci in fish epithelia were more severe in animals exposed to the combined substances, showing slower recovery during depuration. Additionally, the combination treatment yielded unexpected increased expression of a ras-family oncogene homologue after depuration, with evidence for increased tp53 counter-response in the same period. The findings indicate that oncogene expression, cell proliferation and inflammation, may not require noticeable DNA damage to occur. Furthermore, albeit absent proof for neoplasic growth, the removal of chemical insult may promote tissue recovery but does not entirely clear molecular and histopathological endpoints that are commonly associated to neoplasia.
- Explorations on the ecological role of toxin secretion and delivery in jawless predatory PolychaetaPublication . Cuevas, N.; Martins, M.; Rodrigo, A. P.; Martins, C.; Costa, Pedro M.Motivated by biotechnological prospects, there is increasing evidence that we may just be scraping the tip of the iceberg of poisonous marine invertebrates, among which the Polychaeta are promising candidates for bioprospecting. Here we show that an inconspicuous phyllodocid uses toxins in its uncanny feeding strategy. The worm, a jawless active predator characterised by its bright green colour, preys on larger invertebrates (including conspecifics) by extracting tissue portions with its powerful proboscis through suction. The animal is even able to penetrate through the valves and plates of live molluscs and barnacles. Observations in situ and a series of experiments demonstrated that the worm compensates its simple anatomy with secretion of a novel toxin, or mixture of toxins, referred to by us as “phyllotoxins”. These are carried by mucus and delivered via repeated contact with the tip of the proboscis until the prey is relaxed or immobilised (reversibly). Proteolytic action permeabilises material to toxins and softens tissue to enable extraction by suction. The findings show that toxins are a major ecological trait and therefore play a key role in evolutionary success and diversification of Polychaeta, demonstrating also that understanding adaptative features may become the best showcase for novel animal toxins.
- Metabolic and histopathological alterations in the marine bivalve Mytilus galloprovincialis induced by chronic exposure to acrylamidePublication . Larguinho, Miguel; Cordeiro, Ana; Diniz, Mário S.; Costa, Pedro M.; Baptista, Pedro V.Although the neurotoxic and genotoxic potential of acrylamide has been established in freshwater fish, the full breadth of the toxicological consequences induced by this xenobiotic has not yet been disclosed, particularly in aquatic invertebrates. To assess the effects of acrylamide on a bivalve model, the Mediterranean mussel (Mytilus galloprovincialis), two different setups were accomplished: 1) acute exposure to several concentrations of waterborne acrylamide to determine lethality thresholds of the substance and 2) chronic exposure to more reduced acrylamide concentrations to survey phases I and II metabolic endpoints and to perform a whole-body screening for histopathological alterations. Acute toxicity was low (LC50≈400mg/L). However, mussels were responsive to prolonged exposure to chronic concentrations of waterborne acrylamide (1-10mg/L), yielding a significant increase in lipid peroxidation plus EROD and GST activities. Still, total anti-oxidant capacity was not exceeded. In addition, no neurotoxic effects could be determined through acetylcholine esterase (AChE) activity. The findings suggest aryl-hydrocarbon receptor (Ahr)-dependent responses in mussels exposed to acrylamide, although reduced comparatively to vertebrates. No significant histological damage was found in digestive gland or gills but female gonads endured severe necrosis and oocyte atresia. Altogether, the results indicate that acrylamide may induce gonadotoxicity in mussels, although the subject should benefit from further research. Altogether, the findings suggest that the risk of acrylamide to aquatic animals, especially molluscs, may be underestimated.