ABSTRACT
Hyper-O-GlcNAcylation is a general feature of cancer which contributes to various cancer phenotypes, including cell proliferation and cell growth. Quercetin, a naturally occurring dietary flavonoid, has been reported to reduce the proliferation and growth of cancer. Several reports of the anticancer effect of quercetin have been published, but there is no study regarding its effect on O-GlcNAcylation. The aim of this study was to investigate the anticancer effect of quercetin on HeLa cells and compare this with its effect on HaCaT cells. Cell viability and cell death were determined by MTT and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling assays. O-GlcNAcylation of AMP-activated protein kinase (AMPK) was examined by succinylated wheat germ agglutinin pulldown and immunoprecipitation. Immunofluorescence staining was used to detect the immunoreactivitiy of O-linked N-acetylglucosamine transferase (OGT) and sterol regulatory element binding protein 1 (SREBP-1). Quercetin decreased cell proliferation and induced cell death, but its effect on HaCaT cells was lower than that on HeLa cells. O-GlcNAcylation level was higher in HeLa cells than in HaCaT cells. Quercetin decreased the expression of global O-GlcNAcylation and increased AMPK activation by reducing the O-GlcNAcylation of AMPK. AMPK activation due to reduced O-GlcNAcylation of AMPK was confirmed by treatment with 6-diazo-5-oxo-L-norleucine. Our results also demonstrated that quercetin regulated SREBP-1 and its transcriptional targets. Furthermore, immunofluorescence staining showed that quercetin treatment decreased the immunoreactivities of OGT and SREBP-1 in HeLa cells. Our findings demonstrate that quercetin exhibited its anticancer effect by decreasing the O-GlcNAcylation of AMPK. Further studies are needed to explore how quercetin regulates O-GlcNAcylation in cancer.
Subject(s)
Humans , Adenosine , AMP-Activated Protein Kinases , Cell Death , Cell Proliferation , Cell Survival , Deoxyuridine , Diazooxonorleucine , Fluorescent Antibody Technique , HeLa Cells , Immunoprecipitation , Phenotype , Protein Kinases , Quercetin , Sterol Regulatory Element Binding Protein 1 , Transferases , Triticum , Uterine Cervical NeoplasmsABSTRACT
BACKGROUND: Waist circumference and BMI have been known as an independent predictor for cardiovascular diseases. But some people with a normal BMI or normal waist circumference may have cardiovascular risk factors. Therefore, the purpose of this study was to investigate the simplicity and the usefulness of waist/height ratio as an index of obesity and to investigate the waist/height ratio as a predictor for metabolic risks in individuals with normal weight and/or normal waist circumference. METHODS: The subjects were 1,157 individuals (635 men, 522 women). The morbidity index for metabolic risk factors was calculated by the sum of the risk factors scores (one point per item, if present). We set the criteria of obesity as BMI>or=25 kg/m2, waist circumference of >or=90 cm in males and >or=80 cm in females, waist/hip ratio of >or=0.9 in males and >or=0.8 in females, and waist/height ratio of >or=50 cm/cm*100. RESULTS: There was a significant correlation among waist/ height ratio, waist/hip ratio, BMI, and waist circumference (P=0.000). The odds ratios for morbidity index (>or=3) in normal BMI, waist circumference, and waist/hip ratio subjects with waist/height over 50 were significantly higher with 4.60, 3.83, and 2.79, respectively, and also higher in normal BMI with normal waist circumference subjects with 3.90 (P=0.000). CONCLUSION: Waist/height ratio may be used a simple and practical index of obesity. Especially, it may be useful in subjects with normal BMI or normal waist circumference when predicting their metabolic risks.