RESUMO
Breast cancer is one of the most frequent cancers in the population, especially in older women. Estrogen is known to be a key hormone in the development and progression of mammary carcinogenesis. In this study, we investigated if the procarcinogenic effect of 17ß-estradiol (E2) in breast cancer MCF-7 cells is dependent on changes in glucose or folic acid cellular uptake. The effect of E2 on uptake of 3H-deoxy-d-glucose, 3H-folic acid, cell proliferation (3-thymidine incorporation assay), culture growth (sulforhodamine B assay), viability (lactate dehydrogenase activity assay), lactate production and migration capacity (injury assay) was evaluated. E2 (48h; 100nM) increased culture growth (16%), proliferation rate (24%), cellular viability (36%) and lactate production (38%). In contrast, E2 did not significantly affect the migration capacity of MCF-7 cells. The pro-proliferative, but not the cytoprotective effect of E2 was found to be ERß-dependent. The polyphenols rutin and caffeic acid were not able to counteract the effect of E2 upon cell proliferation and viability. Uptake of 3H-deoxy-d-glucose was not affected by E2, either in the absence or presence of GLUT inhibitors (cytochalasin B plus phloridzin). Moreover, E2 did not change GLUT1 mRNA levels. Finally, 3H-folic acid uptake was also not affected by E2, both in the absence and presence of the RFC1 inhibitor, methotrexate. The pro-proliferative and cytoprotective effects of E2 are not dependent neither of stimulation of glucose cellular uptake (both GLUT and non-GLUT-mediated) nor of stimulation of folic acid uptake (both RFC1-and non-RFC1-mediated).
Assuntos
Neoplasias da Mama/induzido quimicamente , Neoplasias da Mama/patologia , Carcinogênese/efeitos dos fármacos , Transformação Celular Neoplásica/efeitos dos fármacos , Estradiol/efeitos adversos , Alimentos/efeitos adversos , Transporte Biológico/efeitos dos fármacos , Ácidos Cafeicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Transformação Celular Neoplásica/metabolismo , Feminino , Glucose/metabolismo , Transportador de Glucose Tipo 1/metabolismo , Humanos , Células MCF-7 , Polifenóis/farmacologia , RNA Mensageiro/metabolismo , Rutina/farmacologiaRESUMO
We aimed to determine the oxidative stress status in placentas obtained from gestational (GDM) and type 1 (T1D) diabetic pregnancies. Malonaldehyde and protein carbonyls, two biomarkers of oxidative damage, were higher in T1D but not in GDM placentas. Also, higher reduced glutathione and lower oxidized glutathione levels and higher glutathione peroxidase activity were found in T1D but not in GDM placentas. These results suggest that T1D placentas may develop a protective antioxidant mechanism to overcome higher oxidative stress levels.
