Helena Marcelino

Scopus Publications

The landscape of taste receptors in glioblastoma
Ana R. Costa, Catarina L. Ferreira, Tânia Bessa-Soares, Ana C. Duarte, Isabel Gonçalves, et al.
Biochemical Pharmacology, 2026
Bitter Taste Signalling via TAS2R43 Enhances Temozolomide Efficacy in Glioblastoma Cells
Ana R. Costa, Ana C. Duarte, Isabel Gonçalves, Robert Preissner, José F. Cascalheira, et al.
International Journal of Molecular Sciences, 2026
Bitter taste receptors (TAS2Rs) are increasingly recognised as extraoral chemosensors that modulate diverse biological processes, including cancer cell behaviour and drug responsiveness. Many TAS2R ligands correspond to therapeutic compounds; however, their contribution to the response of brain tumours to chemotherapy remains unexplored. Here, we investigated whether the bitter taste signalling pathway is modulated by temozolomide (TMZ), the standard chemotherapeutic agent for glioblastoma, with an impact on treatment efficacy in glioblastoma cells. We show that TMZ elicits intracellular Ca2+ responses compatible with activation of G-protein-coupled receptor signalling and induces anti-proliferative and pro-apoptotic effects in multiple human glioblastoma cell lines. Pharmacological inhibition of bitter taste receptors, as well as genetic silencing of the taste transduction G protein GNAT3, significantly attenuated TMZ-induced cytotoxicity, suggesting that bitter taste signalling is involved in this process. In silico ligand prediction combined with receptor expression profiling identified TAS2R43 as a candidate modulator of these effects, and TAS2R43 knockdown markedly reduced TMZ-induced loss of cell viability and apoptosis. Moreover, TMZ enhanced intracellular accumulation of the ABC transporter substrate doxorubicin, suggesting modulation of multidrug efflux mechanisms. Collectively, our findings identify TAS2R43 as a potential biomarker that warrants further validation to improve responses to TMZ and other ABC transporter-limited anticancer drugs.
Therapeutic Potential of Resveratrol for Glioma: A Systematic Review and Meta-Analysis of Animal Model Studies
Ângelo Luís, Helena Marcelino, Fernanda Domingues, Luísa Pereira, José Francisco Cascalheira
International Journal of Molecular Sciences, 2023
Gliomas are aggressive malignant brain tumors, with poor prognosis despite available therapies, raising the necessity for finding new compounds with therapeutic action. Numerous preclinical investigations evaluating resveratrol’s anti-tumor impact in animal models of glioma have been reported; however, the variety of experimental circumstances and results have prevented conclusive findings about resveratrol’s effectiveness. Several databases were searched during May 2023, ten publications were identified, satisfying the inclusion criteria, that assess the effects of resveratrol in murine glioma-bearing xenografts. To determine the efficacy of resveratrol, tumor volume and animal counts were retrieved, and the data were then subjected to a random effects meta-analysis. The influence of different experimental conditions and publication bias on resveratrol efficacy were evaluated. Comparing treated to untreated groups, resveratrol administration decreased the tumor volume. Overall, the effect’s weighted standardized difference in means was −2.046 (95%CI: −3.156 to −0.936; p-value < 0.001). The efficacy of the treatment was observed for animals inoculated with both human glioblastoma or rat glioma cells and for different modes of resveratrol administration. The combined administration of resveratrol and temozolomide was more effective than temozolomide alone. Reducing publication bias did not change the effectiveness of resveratrol treatment. The findings suggest that resveratrol slows the development of tumors in animal glioma models.
Effects of bisphenol A on human umbilical arteries
Nádia Oliveira, Helena Marcelino, Regina Azevedo, Ignacio Verde
Environmental Science and Pollution Research, 2023
Correction to: Effects of bisphenol A on human umbilical arteries (Environmental Science and Pollution Research, (2022), 30, 10, (27670-27681), 10.1007/s11356-022-24069-3)
Nádia Oliveira, Helena Marcelino, Regina Azevedo, Ignacio Verde
Environmental Science and Pollution Research, 2023
Adenosine Inhibits Cell Proliferation Differently in Human Astrocytes and in Glioblastoma Cell Lines
Helena Marcelino, Tiago M.A. Carvalho, Joana Tomás, Francisca I. Teles, Ana C. Honório, et al.
Neuroscience, 2021
Glioblastoma (GBM) is the most common brain primary tumour. Hypoxic regions in GBM are associated to tumour growth. Adenosine accumulates in hypoxic regions and can affect cell proliferation and survival. However, how proliferating GBM cells respond/adapt to increased adenosine levels compared to human astrocytes (HA) is not clarified and was addressed in the present work. GBM cell lines and HA were treated for 3 days with test drugs. 30µM-Adenosine caused a 46%±3% (P<0.05) reduction of cell proliferation/viability in HA, through an adenosine receptor-independent mechanism, but had no effect in glioblastoma cell lines U87MG, U373MG and SNB19. Contrastingly, inhibition of adenosine phosphorylation (using the adenosine kinase (ADK) inhibitor 5-iodotubercidin (25µM)), produced a strong and similar decrease on cell proliferation in both HA and glioblastoma cells. The effect of adenosine on HA proliferation/viability was potentiated by 100µM-homocysteine. Combined application of 30µM-adenosine and 100µM-homocysteine reduced cell proliferation/viability in all three GBM cell lines, but this reduction was much lower than that observed in HA. Adenosine alone did not induce cell death, assessed by LDH release, both in HA and GBM cells, but potentiated cytotoxic effect of homocysteine in HA and in U87MG and U373MG cells. Results show a strong attenuation of adenosine anti-proliferative effect in GBM cells compared to HA, probably resulting from increased adenosine elimination by ADK, suggesting a proliferative-prone adaptation of tumour cells to increased adenosine levels.
Countering impaired glucose homeostasis during catch-up growth with essential polyunsaturated fatty acids: is there a major role for improved insulin sensitivity?
Julie Calonne, Helena Marcelino, Christelle Veyrat-Durebex, Isabelle Scerri, Abdul G. Dulloo
Nutrition and Diabetes, 2021
Background/Objectives Catch-up growth, an important risk factor for later obesity and type 2 diabetes, is often characterized by a high rate of fat deposition associated with hyperinsulinemia and glucose intolerance. We tested here the hypothesis that refeeding on a high-fat diet rich in essential polyunsaturated fatty acids (ePUFA) improves glucose homeostasis primarily by enhancing insulin sensitivity in skeletal muscles and adipose tissues. Methods Rats were caloric restricted for 2 weeks followed by 1–2 weeks of isocaloric refeeding on either a low-fat (LF) diet, a high-fat (HF) diet based on animal fat and high in saturated and monounsaturated fatty acids (HF SMFA diet), or a HF diet based on vegetable oils (1:1 mixture of safflower and linseed oils) and rich in the essential fatty acids linoleic and α-linolenic acids (HF ePUFA diet). In addition to measuring body composition and a test of glucose tolerance, insulin sensitivity was assessed during hyperinsulinemic-euglycemic clamps at the whole-body level and in individual skeletal muscles and adipose tissue depots. Results Compared to animals refed the LF diet, those refed the HF-SMFA diet showed a higher rate of fat deposition, higher plasma insulin and glucose responses during the test of glucose tolerance, and markedly lower insulin-stimulated glucose utilization at the whole body level (by a-third to a-half) and in adipose tissue depots (by 2–5 folds) during insulin clamps. While refeeding on the ePUFA diet prevented the increases in fat mass and in plasma insulin and glucose, the results of insulin clamps revealed that insulin-stimulated glucose utilization was not increased in skeletal muscles and only marginally higher in adipose tissues and at the whole-body level. Conclusions These results suggest only a minor role for enhanced insulin sensitivity in the mechanisms by which diets high in ePUFA improves glucose homeostasis during catch-up growth.
The effects of cannabinoids on glioblastoma growth: A systematic review with meta-analysis of animal model studies
Ângelo Luís, Helena Marcelino, Carolina Rosa, Fernanda Domingues, Luísa Pereira, et al.
European Journal of Pharmacology, 2020
Glioblastoma multiforme (GBM) is the most frequent and aggressive malignant brain tumour, with a poor prognosis despite available surgical and radio-chemotherapy, rising the necessity for searching alternative therapies. Several preclinical studies evaluating the efficacy of cannabinoids in animal models of GBM have been described, but the diversity of experimental conditions and of outcomes hindered definitive conclusions about cannabinoids efficacy. A search in different databases (Pubmed, Web of Science, Scopus and SciELO) was conducted during June 2019 to systematically identify publications evaluating the effects of cannabinoids in murine xenografts models of GBM. The tumour volume and number of animals were extracted, being a random effects meta-analysis of these results performed to estimate the efficacy of cannabinoids. The impact of different experimental factors and publication bias on the efficacy of cannabinoids was also assessed. Nine publications, which satisfied the inclusion criteria, were identified and subdivided in 22 studies involving 301 animals. Overall, cannabinoid therapy reduced the fold of increase in tumour volume in animal models of GBM, when compared with untreated controls. The overall weighted standardized difference in means (WSDM) for the effect of cannabinoids was -1.399 (95% CI: -1.900 to -0.898; P-value<0.0001). Furthermore, treatment efficacy was observed for different types of cannabinoids, alone or in combination, and for different treatment durations. Cannabinoid therapy was still effective after correcting for publication bias. The results indicate that cannabinoids reduce the tumour growth in animal models of GBM, even after accounting for publication bias.
Adenosine inhibits human astrocyte proliferation independently of adenosine receptor activation
Helena Marcelino, Vanda C. Nogueira, Cecília R.A. Santos, Patrícia Quelhas, Tiago M.A. Carvalho, et al.
Journal of Neurochemistry, 2020
Brain adenosine concentrations can reach micromolar concentrations in stressful situations such as stroke, neurodegenerative diseases or hypoxic regions of brain tumours. Adenosine can act by receptor‐independent mechanism by reversing the reaction catalysed by S‐adenosylhomocysteine (SAH) hydrolase, leading to SAH accumulation and inhibition of S‐adenosylmethionine (SAM)‐dependent methyltransferases. Astrocytes are essential in maintaining brain homeostasis but their pathological activation and uncontrolled proliferation plays a role in neurodegeneration and glioma. Adenosine can affect cell proliferation, but the effect of increased adenosine concentration on proliferation of astrocytes is not clarified and was addressed in present work.
Tributyltin role on the serotonin and histamine receptors in human umbilical artery
Solange Glória, João Marques, Joana Feiteiro, Helena Marcelino, Ignacio Verde, et al.
Toxicology in Vitro, 2018
Some studies in animals suggest that TBT may constitute a risk factor for cardiovascular diseases. Hence, the main purpose of this study was to investigate in human umbilical artery (HUA) the effect of TBT on vascular reactivity, manly in serotonin (5-HT) and histamine receptors. Using standard organ bath techniques, rings of HUA without endothelium were contracted by 5-HT and histamine. We also investigated the effect of TBT on the expression of the receptors using Real-time PCR. The results show that TBT short term effects include concentration-dependent relaxation. Moreover, at long term exposures, the arteries treated with 100 μM of TBT do not have contraction capacity when 5-HT is added, and the gene expression of 5-HT2A receptor decrease. Regarding histamine, it was demonstrated that TBT induces a concentration-dependent relaxation and the H1 gene expression levels decrease. In conclusion TBT modifies the activity and expression of 5-HT and histamine receptors.
Sex Hormones Protect Against Amyloid-β Induced Oxidative Stress in the Choroid Plexus Cell Line Z310
A. R. Costa, H. Marcelino, I. Gonçalves, T. Quintela, J. Tomás, et al.
Journal of Neuroendocrinology, 2016
Sex-Related Differences in Rat Choroid Plexus and Cerebrospinal Fluid: A cDNA Microarray and Proteomic Analysis
T. Quintela, H. Marcelino, M. J. Deery, R. Feret, J. Howard, et al.
Journal of Neuroendocrinology, 2016
Gene Expression Profiling in the Hippocampus of Orchidectomized Rats
Telma Quintela, Helena Marcelino, Isabel Gonçalves, Filipa M. Patriarca, Cecília R. A. Santos
Journal of Molecular Neuroscience, 2015
Analysis of the Effects of Sex Hormone Background on the Rat Choroid Plexus Transcriptome by cDNA Microarrays
Telma Quintela, Isabel Gonçalves, Laura C. Carreto, Manuel A. S. Santos, Helena Marcelino, et al.
Plos One, 2013
A role for adipose tissue de novo lipogenesis in glucose homeostasis during catch-up growth: A randle cycle favoring fat storage
Helena Marcelino, Christelle Veyrat-Durebex, Serge Summermatter, Delphine Sarafian, Jennifer Miles-Chan, et al.
Diabetes, 2013
Dietary modulation of body composition and insulin sensitivity during catch-up growth in rats: Effects of oils rich in n-6 or n-3 PUFA
Gayathri Yepuri, Helena Marcelino, Yasaman Shahkhalili, Olivier Aprikian, Katherine Macé, et al.
British Journal of Nutrition, 2011
Adipose tissue plasticity during catch-up fat driven by thrifty metabolism: Relevance for muscle-adipose glucose redistribution during catch-up growth
Serge Summermatter, Helena Marcelino, Denis Arsenijevic, Antony Buchala, Olivier Aprikian, et al.
Diabetes, 2009
New amino and acetamido monomethine cyanine dyes for the detection of DNA in agarose gels
Reda M. El-Shishtawy, Cecília R. Santos, Isabel Gonçalves, Helena Marcelino, Paulo Almeida
Bioorganic and Medicinal Chemistry, 2007