Non-enzymatic glycation of protein induces cancer cell proliferation and its inhibition by quercetin: Spectroscopic, cytotoxicity and molecular docking studies.

Methylglyoxal (MG) is a potent glycating agent which reacts with proteins to form advanced glycation end products (AGEs). These chemically stable AGEs crosslink with proteins and could lead to amyloid formation that has the role in several diseases including Alzheimer's and Parkinson's. In this piece of work, glycation-induced conformational changes in HSA were observed with quenching of tryptophan fluorescence by 73.8% (41 nm red shift) and loss of hydrophobicity of HSA. CD spectroscopy result reaffirmed secondary structure changes in HSA. Moreover, MG-induced changes in HSA, proceeds to amyloid structure as characterized by an increase in thioflavin (ThT) fluorescence and transmission electron microscopy (TEM) images of HSA aggregates. Quercetin was found to inhibit both AGEs production and amyloid formation. Viability of MCF-7 cells was found to be increased with AGEs treatment, illustrating proliferation of cancer cells. Wound healing assay also revealed increased proliferation and migration of cells in the presence of AGEs. Additionally, molecular docking analyses were performed to demonstrate interactions involved in the stabilization of HSA-quercetin complex. The binding affinities of quercetin were found to be (K d = 105 M -1) much higher compared with MG (K d = 102 M -1). From this study, it is quite clear that quercetin reverses the effect of MG by sterically inhibiting the interaction between HSA and MG. Communicated by Ramaswamy H. Sarma.

Severe hypovitaminosis D is widespread and more common in non-diabetics than diabetics in Saudi adults.

OBJECTIVE: To compare the incidence of hypovitaminosis D in subjects, with and without type 2 diabetes mellitus (T2DM), and determine its association to various risk factors. METHODS: Three hundred and forty-one (177 non-diabetic, and 164 T2DM) Saudi adults were included in this cross-sectional study conducted at the Biomarkers Research Program (BRP) of King Saud University, Riyadh, Kingdom of Saudi Arabia from March to August 2009. Anthropometrics and fasting blood samples were obtained. Fasting glucose (FG) and lipid profiles were determined. Serum 25-hydroxy vitamin D (25[OH]D) and parathyroid hormone (PTH) were quantified using enzyme-linked immunosorbent assay. Severe hypovitaminosis D was defined as serum 25(OH)D with levels <12.5 nmol/l. RESULTS: Age was the most significant predictor of 25(OH)D in both groups, explaining 25% (p=0.0005) and 16% of variances (p=0.0005). Waist-hip ratio, systolic blood pressure and body mass index were significant predictors of 25(OH)D among non-diabetics after age adjustment, explaining 21% of variance perceived (p=0.039). Serum PTH levels were higher in non-diabetic men and women. CONCLUSION: Severe hypovitaminosis D is prevalent in both non-diabetic and diabetic Saudis, but was more common in the young and middle-aged non-diabetics. The study further underscores the need for vitamin D fortification of the Saudi diet, and the promotion of vitamin D supplementation in both groups.