RESUMEN
The purpose of the current study was to develop and test a theoretical model that could explain the mechanism of action of gallic acid (GA) in the oral squamous cell carcinoma context for the first time. The theoretical model was developed using bioinformatics and interaction network analysis to evaluate the effect of GA on oral squamous cell carcinoma. In a second step to confirm theoretical results, migration, invasion, proliferation, and gene expression (Col1A1, E-cadherin, HIF-1α, and caspase-3) were performed under normoxic and hypoxic conditions. Our study indicated that treatment with GA resulted in the inhibition of cell proliferation, migration, and invasion in neoplastic cells. Observation of the molecular mechanism showed that GA upregulates E-cadherin expression and downregulates Col1A1 and HIF-1α expression, suggesting that GA might be a potential anticancer compound. In conclusion, the present study demonstrated that GA significantly reduces cell proliferation, invasion, and migration by increasing E-cadherin and repressing Col1A1.
Asunto(s)
Antineoplásicos/farmacología , Carcinoma de Células Escamosas/tratamiento farmacológico , Ácido Gálico/farmacología , Modelos Biológicos , Neoplasias de la Boca/tratamiento farmacológico , Cadherinas/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Caspasa 3/metabolismo , Hipoxia de la Célula , Línea Celular Tumoral/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Colágeno Tipo I/metabolismo , Cadena alfa 1 del Colágeno Tipo I , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/patología , Invasividad NeoplásicaRESUMEN
The expression of metalloproteinases and their inhibitors has been related to different invasive and metastatic potentials in cancer. This study aims to investigate the immunohistochemical expression of TIMP-3 and MMP-9 in samples of basal cell carcinoma (BCC), squamous cell carcinoma of the skin (SCC), and actinic keratosis (AK). Immunohistochemistry was performed to evaluate the expression of TIMP-3 and MMP-9 in samples of BCC (n=22), SCC (n=10), and AK (n=15). Ten fields of both tumor parenchyma and tumor stroma were photographed and counted in image software. The ratio of positive cells to total cells was used to quantify the staining. A higher expression of MMP-9 was found in tumor stroma of SCC compared to BCC and AK. No significant differences in TIMP-3 expression were observed among the groups. Considering the well-described differences between these neoplasms, these results provide additional evidence of the role of MMP-9 in tumor invasiveness of keratinocyte-derived tumors.
Asunto(s)
Biomarcadores de Tumor/análisis , Carcinoma Basocelular/enzimología , Carcinoma de Células Escamosas/enzimología , Inmunohistoquímica , Queratosis Actínica/enzimología , Metaloproteinasa 9 de la Matriz/análisis , Neoplasias Cutáneas/enzimología , Inhibidor Tisular de Metaloproteinasa-3/análisis , Adulto , Anciano , Carcinoma Basocelular/patología , Carcinoma de Células Escamosas/patología , Femenino , Humanos , Queratosis Actínica/patología , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Neoplasias Cutáneas/patologíaRESUMEN
OBJECTIVE: The aim of this study was to evaluate the expression of RAS components and SIRTs enzymes in the adipose tissue of mice fed diets with different macronutrient composition. DESIGN AND METHODS: The body weight, food intake, and energy intake (kcal) were evaluated. Blood parameters (insulin sensitivity, glucose tolerance, total cholesterol, HDL-C triglyceride, and glucose levels) were also assessed. Real-time PCR was performed in epididymal adipose tissue samples to analyze the expression of renin, angiotensinogen (AGT), angiotensin-converting enzyme 1 and 2 (ACE and ACE2), and SIRTs 1-7. Male FVB/N mice were divided into 5 groups (N = 10 each) that were fed with experimental diets for 60 days. Test diets were divided into standard (ST), AIN-93M, high glucose (HG), high protein (HP) and high lipid (HL). RESULTS: The main results showed that HL diet treatment induced reduction in HDL-C and triglyceride plasma levels; increased ACE (Ang II marker) expression and decreased ACE2 (Ang-[1-7] catalyzer) expression in adipose tissue; and also increased SIRT4 expression. CONCLUSION: Diets with high lipid content induced a degenerative state associated with deregulation of adipose tissue enzymes expression.