Browsing by Author "Alves, Marco G."
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- The impact of metabolic syndrome and type 2 diabetes Mellitus on prostate cancerPublication . Sousa, André P.; Costa, Raquel; Alves, Marco G.; Soares, Raquel; Baylina, Pilar; Fernandes, RúbenProstate cancer (PCa) remains the second most common type of cancer in men worldwide in 2020. Despite its low death rate, the need for new therapies or prevention strategies is critical. The prostate carcinogenesis process is complex and multifactorial. PCa is caused by a variety of mutations and carcinogenic events that constitutes the disease’s multifactorial focus, capable of not only remodeling cellular activity, but also modeling metabolic pathways to allow adaptation to the nutritional requirements of the tumor, creating a propitious microenvironment. Some risk factors have been linked to the development of PCa, including Metabolic Syndrome (MetS) and Type 2 Diabetes Mellitus (T2DM). MetS is intrinsically related to PCa carcinogenic development, increasing its aggressiveness. On the other hand, T2DM has the opposite impact, although in other carcinomas its effect is similar to the MetS. Although these two metabolic disorders may share some developmental processes, such as obesity, insulin resistance, and dyslipidemia, their influence on PCa prognosis appears to have an inverse effect, which makes this a paradox. Understanding the phenomena behind this paradoxical behavior may lead to new concepts into the comprehension of the diseases, as well as to evaluate new therapeutical targets. Thus, this review aimed to evaluate the impact of metabolic disorders in PCa’s aggressiveness state and metabolism
- The influence of adipocyte secretome on selected metabolic fingerprints of breast cancer cell lines representing the four major breast cancer subtypesPublication . Luís, Carla; Guerra-Carvalho, Bárbara; Braga, Patrícia C.; Guedes, Carla; Patrício, Emília; Alves, Marco G.; Fernandes, Ruben; Soares, RaquelMolecular subtype (MS) is one of the most used classifications of breast cancer (BC). Four MSs are widely accepted according to receptor expression of estrogen, progesterone, and HER2. The impact of adipose tissue on BC MS metabolic impairment is still unclear. The present work aims to elucidate the metabolic alterations in breast cancer cell lines representing different MSs subjected to adipocyte associated factors. Preadipocytes isolated from human subcutaneous adipose tissue were differentiated into mature adipocytes. MS representative cell lines were exposed to mature adipocyte secretome. Extracellular medium was collected for metabolomics and RNA was extracted to evaluate enzymatic expression by RT-PCR. Adipocyte secretome exposure resulted in a decrease in the Warburg effect rate and an increase in cholesterol release. HER2+ cell lines (BT-474 and SK-BR-3) exhibited a similar metabolic pattern, in contrast to luminal A (MCF-7) and triple negative (TN) (MDA-MB-231), both presenting identical metabolisms. Anaplerosis was found in luminal A and TN representative cells, whereas cataplerotic reactions were likely to occur in HER2+ cell lines. Our results indicate that adipocyte secretome affects the central metabolism distinctly in each BC MS representative cell line.
- Warburg Effect Inversion: Adiposity shifts central primary metabolism in MCF-7 breast cancer cellsPublication . Luís, Carla; Duarte, Fernanda; Faria, Isabel; Jarak, Ivana; Oliveira, Pedro F.; Alves, Marco G.; Soares, Raquel; Fernandes, RúbenObesity is a complex health disorder and a trigger to many diseases like Diabetes mellitus (DM) and breast cancer (BrCa), both leading causes of morbidity and mortality worldwide. Also evidence demonstrates that abnormal glucose metabolism termed ‘the Warburg effect’ in cancer cell is closely associated with malignant phenotypes and promote the aggressiveness of several types of cancer, including BrCa. In this study, we evaluated the breast cancer cell metabolism in normoglycemia, hyperglycemia and in an obesity condition in order to clarify the potential underlined mechanisms that link these disorders. Materials and methods MCF-7 cells were exposed to low and high glucose levels, the latter either in the presence of 3T3-L1 adipocyte conditioned medium (CM), thus mimicking the adiposity observed in obese patients. Cell viability, migration, proliferation, cytotoxicity and cell death assays were performed under the different culture conditions. Hormonal and lipid profile were also characterized by biochemical assays and primary metabolism was determined by Nuclear Magnetic Resonance (NMR)-based metabolomics. Results Our results show an increased aggressiveness in the condition mimicking diabetogenic obesity with an altered energy/lipid metabolism. Interestingly in the experimental obesity-mimicking status, lipids and amino acids were expended while glucose was produced by tumor cells from lactate. These findings reveal a shift on tumor cells metabolism that is opposite to ‘the Warburg effect’. Conclusions Overall, this experimentally obesity-mimicking condition not only revealed an increased tumor proliferation and aggressiveness but also disclosed a new mechanism of cancer metabolism, the ‘Warburg Effect Inversion’.