The effects of Juglone-Selenium combination on invasion and metastasis in pancreatic cancer cell lines

Background: Pancreatic cancer does not show any symptoms in the early period and metastatic process is already passed when the diagnosis is done. Therefore, in the battle with pancreatic cancer, novel treatment strategies, particularly antiinvasive and antimetastatic strategies, are needed. The cytotoxic and anticancer effects of juglone and sodium selenite (NaSe) have been showed in various cancer cells. Objectives: In this study, it is aimed to investigate the synergistic effects of juglone and selenium on PANC-1 and BxPC-3 pancreatic cancer cells. Methods: Antimetastatic effects of juglone-NaSe were carried out by adhesion and invasion assays and the genes and protein expressions. Expression analysis of the CDH1, ITGB3 and COL4A3 genes and their proteins E-cadherin, β3 integrin and tumstatin which play role in metastasis and angiogenesis processes, were done by qPCR and immunohistochemical analysis, respectively. Results: Study findings have provided evidences that the juglone-selenium has a cytotoxic and dose dependent suppressive effect on invasion and metastasis in PANC-1 and BxPC-3 cells. Conclusion: The juglone-NaSe has the potential to be a promising agent especially to inhibit invasion and metastasis in pancreatic cancer treatment. However, more in depth studies are needed to more clearly demonstrate the effects of juglone-selenium. Keywords: Pancreatic cancer cell lines; juglone-selenium; invasion; metastasis

Transcription factor 7-like 2 (TCF7L2) gene polymorphisms are strong predictors of type 2 diabetes among nonobese diabetics in the Turkish population

WOS: 000395632600003PubMed ID: 28263491Background/aim: Type 2 diabetes (T2D) is a multifactorial disease, determined by environmental and genetic factors. Currently, the transcription factor 7-like 2 (TCF7L2) gene shows the strongest association with T2D. In this study, we investigated whether TCF7L2 gene polymorphisms are associated with T2D in a Turkish population. Materials and methods: Using PCR-RFLP and PCR-SSCP, we genotyped six intronic polymorphisms in the TCF7L2 gene, commonly associated with T2D, in 169 individuals with diabetes and 119 healthy controls. Results: We found that rs7903146 C -> T substitution in intron 3 (OR: 1.9, P = 0.005) and rs12255372 G -> T substitution in intron 4 (OR: 2.1, P = 0.002) were significantly associated with T2D while other SNPs were not associated (P > 0.05). We determined no association between TCF7L2 gene polymorphisms and fasting glucose, fasting insulin, HbA1c, or HOMA-IR levels (P > 0.05), except for rs7903146 C -> T substitution, which was significantly associated with the fasting glucose level (P = 0.003). Conclusion: Our results indicate that, in the Turkish population, the T allele of the rs7903146 (C -> T) and rs12255372 (G -> T) polymorphisms in the TCF7L2 gene is an independent risk factor for the development of T2D.Selcuk University Research Foundation [09202048]We would like to thank Dr Hulya Ozdemir and Dr Suleyman Hilmi Ipekci for their assistance in this study. This study was supported by the Selcuk University Research Foundation (09202048)

The Adiponectin variants contribute to the genetic background of type 2 diabetes in Turkish population

Adiponectin, an adipose tissue specific protein encoded by the Adiponectin gene, modulates insulin sensitivity and plays an important role in regulating energy homeostasis. Many studies have shown that single nucleotide polymorphisms (SNPs) in the Adiponectin gene are associated with low plasma Adiponectin levels, insulin resistance and an increased risk of type 2 diabetes mellitus. The aim of the present study was to evaluate the contribution of the Adiponectin gene polymorphisms in genetic background of type 2 diabetes in a Turkish population. In total, 169 unrelated and non-obese diabetic patients and 119 age- and BMI-matched nondiabetic individuals with no family history of diabetes were enrolled in this study. We detected a significant association between type 2 diabetes and two SNPs: SNP - 11391G>A. which is located in the promoter region of the Adiponectin gene, and SNP + 276G > T, which is found in intron 2 of the gene (P G) in exon 1 and SNP + 349A > G in intron 2 also showed a weak association with type 2 diabetes (P = 0.06 and P = 0.07, respectively), while SNPs - 3971A>G in intron 1 and Y111H, R112C and H241P in exon 3 showed no association (P > 0.05). In conclusion, these findings suggest that Adiponectin gene polymorphisms might be effective on susceptibility for type 2 diabetes development which emerged from the interactions between multiple genes, variants and environmental factors. (C) 2013 Elsevier B.V. All rights reserved

Effects of Single Nucleotide Polymorphisms in K-ATP Channel Genes on Type 2 Diabetes in a Turkish Population

Background and Aims. ATP-sensitive potassium (K-ATP) channels of pancreatic beta-cells play a key role in glucose-stimulated insulin secretion mechanism. The Kir6.2 protein, forming the K-ATP channel pore inwardly, and the SUR1 protein that surrounds it forming the outside part of the channel were encoded by ABCC8 and KCNJ11 genes, respectively. Recent studies reported that the single nucleotide polymorphisms (SNPs) established in these genes are associated with defects in insulin secretion and type 2 diabetes mellitus (T2DM). We aimed to investigate the allele profiles and the risk alleles of the ABCC8 and KCNJ11 genes and to highlight the associations with the disease in patients in Konya region of Turkey where T2DM is common

Type 2 diabetes is associated with the MTNR1B gene, a genetic bridge between circadian rhythm and glucose metabolism, in a Turkish population

Type 2 diabetes (T2D) is a complicated public health problem in Turkey as well as worldwide. Genome-wide approaches have been guiding in very challenging situations, such as the elucidation of genetic variations underlying complex diseases such as T2D. Despite intensive studies worldwide, few studies have determined the genetic susceptibility to T2D in Turkish populations. In this study, we investigated the effect of genes that are strongly associated with T2D in genome-wide association (GWA) studies, including MTNR1B, CDKAL1, THADA, ADAMTS9 and ENPP1, on T2D and its characteristic traits in a Turkish population. In 824 nonobese individuals (454 T2D patients and 370 healthy individuals), prominent variants of these GWA genes were genotyped by real-time PCR using the LightSNiP Genotyping Assay System. The SNP rs1387153 C/T, which is located 28 kb upstream of the MTNR1B gene, was significantly associated with T2D and fasting blood glucose levels (P < 0.05). The intronic SNP rs10830963 C/G in the MTNR1B gene was not associated with T2D, but it was associated with fasting blood glucose, HbA1C and LDL levels (P < 0.05). The other important GWA loci investigated in our study were not found to be associated with T2D or its traits. Only the SNP rs1044498 (A/C variation) in the ENPP1 gene was determined to be related to fasting blood glucose (P < 0.05). Our study suggests, consistent with the literature, that the MTNR1B locus, which has a prominent role in glucose regulation, is associated with T2D development by affecting blood glucose levels in our population

Type 2 diabetes is associated with the MTNR1B gene, a genetic bridge between circadian rhythm and glucose metabolism, in a Turkish population

Type 2 diabetes (T2D) is a complicated public health problem in Turkey as well as worldwide. Genome-wide approaches have been guiding in very challenging situations, such as the elucidation of genetic variations underlying complex diseases such as T2D. Despite intensive studies worldwide, few studies have determined the genetic susceptibility to T2D in Turkish populations. In this study, we investigated the effect of genes that are strongly associated with T2D in genome-wide association (GWA) studies, including MTNR1B, CDKAL1, THADA, ADAMTS9 and ENPP1, on T2D and its characteristic traits in a Turkish population. In 824 nonobese individuals (454 T2D patients and 370 healthy individuals), prominent variants of these GWA genes were genotyped by real-time PCR using the LightSNiP Genotyping Assay System. The SNP rs1387153 C/T, which is located 28 kb upstream of the MTNR1B gene, was significantly associated with T2D and fasting blood glucose levels (P < 0.05). The intronic SNP rs10830963 C/G in the MTNR1B gene was not associated with T2D, but it was associated with fasting blood glucose, HbA1C and LDL levels (P < 0.05). The other important GWA loci investigated in our study were not found to be associated with T2D or its traits. Only the SNP rs1044498 (A/C variation) in the ENPP1 gene was determined to be related to fasting blood glucose (P < 0.05). Our study suggests, consistent with the literature, that the MTNR1B locus, which has a prominent role in glucose regulation, is associated with T2D development by affecting blood glucose levels in our population.Scientific and Technological Research Council of Turkey [213S035]This study was supported by the Scientific and Technological Research Council of Turkey (213S035)