RESUMEN
Cancer cells present a particular metabolic behavior. We hypothesized that the progression of bladder cancer could be accompanied by changes in cells glycolytic profile. We studied two human bladder cancer cells, RT4 and TCCSUP, in which the latter represents a more invasive stage. The levels of glucose, pyruvate, alanine and lactate in the extracellular media were measured by Proton Nuclear Magnetic Resonance. The protein expression levels of glucose transporters 1 (GLUT1) and 3 (GLUT3), monocarboxylate transporter 4 (MCT4), phosphofructokinase-1 (PFK1), glutamic-pyruvate transaminase (GPT) and lactate dehydrogenase (LDH) were determined. Our data showed that glucose consumption and GLUT3 levels were similar in both cell lines, but TCCSUP cells displayed lower levels of GLUT1 and PFK expression. An increase in pyruvate consumption, concordant with the higher levels of lactate and alanine production, was also detected in TCCSUP cells. Moreover, TCCSUP cells presented lower protein expression levels of GPT and LDH. These results illustrate that bladder cancer progression is associated with alterations in cells glycolytic profile, namely the switch from glucose to pyruvate consumption in the more aggressive stage. This may be useful to develop new therapies and to identify biomarkers for cancer progression.
Asunto(s)
Glucosa/metabolismo , Glucólisis/fisiología , Ácido Pirúvico/metabolismo , Neoplasias de la Vejiga Urinaria/patología , Alanina/metabolismo , Alanina Transaminasa/biosíntesis , Línea Celular Tumoral , Progresión de la Enfermedad , Transportador de Glucosa de Tipo 1/biosíntesis , Transportador de Glucosa de Tipo 3/biosíntesis , Humanos , L-Lactato Deshidrogenasa/biosíntesis , Ácido Láctico/metabolismo , Transportadores de Ácidos Monocarboxílicos/biosíntesis , Proteínas Musculares/biosíntesis , Invasividad Neoplásica , Estadificación de Neoplasias , Fosfofructoquinasa-1/biosíntesis , Neoplasias de la Vejiga Urinaria/metabolismoRESUMEN
Diabetes mellitus (DM) is a major public health problem and its incidence is rising dramatically. The brain, particularly the cerebral cortex, is very susceptible to glucose fluctuations and hyperglycaemia-induced oxidative stress. Tea (Camellia sinensis (L.)) is widely consumed; however, the antidiabetic properties of white tea remain largely unexplored. In the present study, we investigated the effects of daily consumption of white tea on the cerebral cortex of prediabetic rats. The cerebral cortex metabolic profile was evaluated, and the expression levels of GLUT, phosphofructokinase-1, lactate dehydrogenase (LDH) and monocarboxylate transporter 4 were assessed. LDH activity was also determined. The cerebral cortex oxidative profile was determined by evaluating its antioxidant power, lipid peroxidation and protein oxidation levels. Catalase, glutathione, glutamate, N-acetylaspartate, aspartate, choline, γ-aminobutyric acid, taurine and valine contents were determined. Daily consumption of white tea ameliorated glucose tolerance and insulin sensitivity. Moreover, white tea altered the cortex glycolytic profile, modulating GLUT expression and lactate and alanine contents. Finally, white tea consumption restored protein oxidation and lipid peroxidation levels and catalase expression, and improved antioxidant capacity. In conclusion, daily consumption of white tea improved the cerebral cortex metabolic and oxidative profile in prediabetic rats, suggesting it as a good, safe and inexpensive strategy to prevent DM-related effects in the cerebral cortex.
Asunto(s)
Camellia sinensis/química , Corteza Cerebral/metabolismo , Neuronas/metabolismo , Hojas de la Planta/química , Brotes de la Planta/química , Estado Prediabético/dietoterapia , Té , Animales , Biomarcadores/metabolismo , Camellia sinensis/crecimiento & desarrollo , Corteza Cerebral/enzimología , Regulación de la Expresión Génica , Glutatión/metabolismo , Glucólisis , Resistencia a la Insulina , Peroxidación de Lípido , Masculino , Proteínas del Tejido Nervioso/química , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Neuronas/enzimología , Oxidación-Reducción , Estrés Oxidativo , Oxidorreductasas/genética , Oxidorreductasas/metabolismo , Hojas de la Planta/crecimiento & desarrollo , Brotes de la Planta/crecimiento & desarrollo , Estado Prediabético/enzimología , Estado Prediabético/metabolismo , Carbonilación Proteica , Distribución Aleatoria , Ratas Wistar , Té/efectos adversosRESUMEN
The leaves of Camellia sinensis (L.) are the source of tea, the second most consumed beverage worldwide. Tea contains several chemical compounds such as polyphenols (mainly catechins), caffeine, theophylline, L-theanine, among many others. Polyphenolic compounds are mainly responsible for its significant antioxidant properties and anticarcinogenic potential. Bladder cancer is one of the most common types of cancer, and its progression and onset are thought to be controlled by dietary and lifestyle factors. Epidemiological studies showed that the regular consumption of tea can be a preventive factor for this type of cancer, and several in vivo and in vitro studies reported that tea and its components may interfere in the cancer cells' signaling, preventing the bladder tumor progression. The mechanisms responsible for this protection include deregulation of cell cycle, induction of apoptosis while protecting the surrounding healthy bladder cells, inhibition of metastization processes, among others. Herein, we discuss the potential beneficial effects of tea and tea components in bladder cancer prevention and/or treatment, and how they can be helpful in finding new therapeutic strategies to treat this type of cancer.