RESUMEN
Primary effusion lymphoma (PEL) is an aggressive neoplasm correlated with human herpesvirus 8 (HHV8). Metabolic reprogramming is a hallmark of cancers. The alterations in cellular metabolism are important to the survival of HHV8 latently infected cells. Pyruvate dehydrogenase (PDH) controls the flux of metabolites between glycolysis and the tricarboxylic acid cycle (TCA cycle) and is a key enzyme in cancer metabolic reprogramming. Glutaminolysis is required for the survival of PEL cells. Glutamate dehydrogenase 1 (GDH1) converts glutamate into α-ketoglutarate supplying the TCA cycle with intermediates to support anaplerosis. Previously we have observed that epigallocatechin-3-gallate (EGCG) can induce PEL cell death and N-acetyl cysteine (NAC) attenuates EGCG induced PEL cell death. In this study, results showed that EGCG upregulated the expression of glucose transporter GLUT3, and reduced the expression of pyruvate dehydrogenase E1-alpha (PDHA1), the major regulator of PDH, and GDH1. NAC could partially reverse the effects of EGCG in PEL cells. Overexpression of PDHA1 in PEL cells or supplement of α-ketoglutarate attenuated EGCG induced cell death. EGCG also reduced the levels of oncometabolite D-2-hydroxyglutarate (D2HG). These results suggest that EGCG may modulate the metabolism of PEL cells leading to cell death.
Asunto(s)
Catequina/análogos & derivados , Herpesvirus Humano 8 , Linfoma de Efusión Primaria/metabolismo , Redes y Vías Metabólicas/efectos de los fármacos , Piruvato Deshidrogenasa (Lipoamida)/genética , Catequina/farmacología , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Glutaratos/metabolismo , Humanos , Linfoma de Efusión Primaria/genética , Linfoma de Efusión Primaria/virologíaRESUMEN
A case-control study was conducted to investigate the association between the consumption of local common foods that are rich in vitamin A and the risk of lung cancer in Taiwan. A total of 301 incident lung cancer cases, 602 hospital controls, and 602 neighborhood controls were recruited. The consumption of 13 food items and vitamin supplements was estimated by use of a food frequency questionnaire. The conditional logistic regression models were used to estimate the adjusted odds ratios (AOR) and 95% confidence intervals (CI) for lung cancer risk with each control group as reference by adjustment of covariates. A reduced risk for lung cancer was found to be associated with increased intakes of vitamin A, alpha-carotene, and beta-carotene from 13 food items. More servings of vegetables (AOR for the highest versus the lowest quartile = 0.67-0.70, 95% CI = 0.42-1.08, (plinear trend )= 0.04), garland chrysanthemum (AOR for the highest versus the lowest tertile = 0.58-0.74, 95% CI = 0.37-1.14, (plinear trend )<= 0.04) and sweet potato leaves (AOR for the highest versus the lowest tertile = 0.43-0.65, 95% CI = 0.28-0.96, (plinear trend )<= 0.03) were associated with the reduced risk for lung cancer. In conclusion, higher consumption of vitamin A-rich vegetables, especially garland chrysanthemum and sweet potato leaves might provide potential protection from lung cancer.