G protein gene variants in schizophrenia

Various studies demonstrating enhanced vulnerability to apoptosis may contribute to the pathobiology of schizophrenia. Objective: Thus, G proteins may provide an intriguing link between the signal transduction, and apoptotic hypotheses of schizophrenia. In the light of these findings, we investigated whether G protein gene polymorphisms (GNAS1-T393C and GNB3-C825T) accounted for an increased risk of schizophrenia. Methods: The present analyses were based on 100 subjects diagnosed with schizophrenia, and on 100 unrelated healthy controls. The genotyping of GNAS1-T393C, and GNB3-C825T gene polymorphisms were performed using the polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP). Results: We demonstrated the positive association of GNB3-C825T gene variants with schizophrenia risk (p: 0.023). In our study, more prevalent CC genotype frequencies were detected in GNB3 in patients compared with the frequencies in the controls. The individuals with GNB3-C825T CC genotype had 2 fold increased risk for schizophrenia (p: 0.011, c2: 6.39, OR:2.14, 95% CI: 1.18-3.90). Discussion: Our study results suggested that GNB3-C825T polymorphism might be associated with schizophrenia

A new target for the treatment of endometrium cancer by succinic acid

Endometrium cancer is the most common invasive gynecologic malignancy in developed countries. Succinic acid (CO2HCH2-CH2CO2H) is a type of dibasic acid that has uncolored crystal. Succinic acid is used in bakery products and aromatized products. It is naturally found in some vegetables. Succinic acid has no adverse effects because it is metabolized by body cells and has a role in the tricarboxylic acid cycle (TCA) as a cycle media component. The TCA cycle and its enzyme components have some crucial roles for basal cell metabolism. Any mistakes, concentration differences in product, or enzyme deficiencies are important within the cell this cycle. In this proposal project, we aimed to investigate the effect of succinic acid at different doses and at different times in an endometrial cancer cell line. The study was performed using methods that determine for apoptosis (for cytotoxicity, WST-1, for caspase enzyme activity, Caspase 3/BCA; apoptotic determination using flow cytometry; Annexin V; to understand mitochondrial membrane potential; JC-1). The results showed that 5 and 10 mu M concentration of succinic acid resulted in apoptosis in endometrium cancer; no such effect was seen in the control cell line, which comprised healthy lung cells. According to our results, it is thought that succinic acid would be effective for the treatment of endometrial cancer cell lines, thus providing new data for other areas of cancer research

A new target for the treatment of endometrium cancer by succinic acid

Endometrium cancer is the most common invasive gynecologic malignancy in developed countries. Succinic acid (CO2HCH2-CH2CO2H) is a type of dibasic acid that has uncolored crystal. Succinic acid is used in bakery products and aromatized products. It is naturally found in some vegetables. Succinic acid has no adverse effects because it is metabolized by body cells and has a role in the tricarboxylic acid cycle (TCA) as a cycle media component. The TCA cycle and its enzyme components have some crucial roles for basal cell metabolism. Any mistakes, concentration differences in product, or enzyme deficiencies are important within the cell this cycle. In this proposal project, we aimed to investigate the effect of succinic acid at different doses and at different times in an endometrial cancer cell line. The study was performed using methods that determine for apoptosis (for cytotoxicity, WST-1, for caspase enzyme activity, Caspase 3/BCA; apoptotic determination using flow cytometry; Annexin V; to understand mitochondrial membrane potential; JC-1). The results showed that 5 and 10 mu M concentration of succinic acid resulted in apoptosis in endometrium cancer; no such effect was seen in the control cell line, which comprised healthy lung cells. According to our results, it is thought that succinic acid would be effective for the treatment of endometrial cancer cell lines, thus providing new data for other areas of cancer research

The apoptotic efficacy of succinic acid on renal cancer cell lines

Recently, studies on the effects of non-toxic substances on cancer prophylaxis have gained value as an alternative to existing treatment options. Current studies have shown that succinic acid or its derivatives exhibit anticancer activity by inducing apoptosis. We aimed to investigate the anticancer activity of succinic acid on renal cancer for the first time in the literature. The cytotoxic activity of succinic acid on CAKI-2 and ACHN as renal cancer cell lines and MRC-5 as a healthy cell line was determined using the WST-1 cytotoxicity test. Apoptotic activity was measured by Annexin V test and cell death ELISA kit. The results showed that 25 mu M and 50 mu M doses of succinic acid for 24 h remarkably reduced the cell viability for CAKI-2 cells (89.77% and 90.77%) and ACHN cells (41.57% and 54.54%). Also, no significant effect was observed on the healthy cell line, as we expected. Additionally, administration of succinic acid at same doses resulted in apoptotic activity for ACHN cells (19.1 and 12.7) and CAKI-2 cells (19.85 and 29.55). ELISA results with same doses of succinic acid treatment increased the apoptotic fragment rates by 4.7 and 2.13-fold in CAKI-2 cells, and 32.92, 12.7-fold in ACHN cells. Succinic acid is a focal point for cancer treatments not only for its apoptotic success on cancer cells but also for its capacity to be metabolically active for humans. Our results suggest that succinic acid could be a potential therapeutic agent for individual cancer treatment approaches together with further molecular research

Hesperidin triggering apoptosis on neuroblastoma cell

Aim: Neuroblastoma accounts for approximately %10 of all pediatric cancers and approximately %15 of cancer related deaths in children. Understanding of the molecular mechanisms which play role in the progress of this cancer type may lead to develop more effective strategies for therapy. Flavanoids are popular subject for this new strategies. Hesperidin is an herbal flavonoid which is found abundantly in citrus that has been studied on several cancer cell lines. For this purpose, it was aimed to investigate is the apoptotic effects of hesperidin on neuroblastoma tumors using SH-SY5Y cell line.Methods: Hesperidin was performed on SH-SY5Y and MRC-5 cell line by WST-1, Caspase-3 and Annexin V in a time and dose dependent manner. Results: 2.5 µM hesperidin and 5 µM hesperidin were found the most suitable dosage for neuroblastoma cell line because of the success on decreasing cell proliferation. Hesperidin has resulted with the ability for apoptotic cell death compared with control group [MRC-5 cell line, p<0.05 for all]. 2,5 µM and 5 µM hesperidin concentration for 48h were ended up early apoptotic results as 53.65% for 2.5 µM and 38.90% for 5 µM. There was no significant change on caspase-3 activity. Conclusions: Our study suggests that hesperidin would be effective against neuroblastoma tumors. We believe with further investigation this study will be helpful for developing new research areas in neuroblastoma tumors

Apoptotic effects of acacetin in human colon cancer HT‑29 and HCT 116 cells

Aim: Acacetin is a natural flavone compound, which is found in several plants as Robinia pseudoacacia and is demonstrated to haveanticancerogenic activities in many types of cancer (e.g., human nonsmall cell lung cancer, and prostate). Colorectal carcinoma (CRC)is one of the serious health problems and is a complex disease. We intended to find a more effective new candidate for the treatmentof colon cancer, and hence, we designed this study to investigate the effects of acacetin on CRC (HT‑29, HCT 116) in vitro.Methods: The study was carried out with the methods that determine for apoptosis (WST‑1, Caspase 3/BCA, Annexin V).Results: Acacetin showed antitumor and apoptosis‑inducing effects in the CRC cell lines.Conclusions: Acacetin was effective on CRC cell lines, besides no lethal effect on healthy lung cells (MRC‑5)

Assessment of the role of EGF +61A/G and EGFR R497K polymorphism in patients with inflammatory bowel disease: A case-control study

Aim: Epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) play an important role in the regulation of cell growth, survival, migration, apoptosis, proliferation, and differentiation. We aimed to investigate the presence of EGF (+61A/G) and EGFR R497Kpolymorphisms in patients with inflammatory bowel disease (IBD) and their associations with clinical features of the patients.Methods: This case-control study included 91 IBD patients (45 Crohn’s disease (CD) patients and 46 ulcerative colitis (UC) patients) and 129 healthy controls (HC).  EGF and EGFR were genotyped by polymerase chain reaction and restriction fragment length polymorphism techniques to elucidate their association with clinical outcomes. The disease activity for UC and CD were assessed by Truelove-Witts index (TW) and Crohn's disease activity index (CDAI), respectively. The Montreal classification was used for disease involvement and behavior.Results: EGFR497 AA genotype was significantly decreased in patients with UC compared with CD and HC. In addition, the patients with UC who had EGF +61 A allele had increased risk of moderate and severe disease (p=0.28; OR= 3.13; 95% CI=0.34-28.73). The patients with CD who had the EGF61 AG genotype were found to increased risk for the presence of penetrating disease (p=0.14; χ2=5.59; OR=5.00; 95% CI=1.26-19.83). EGF +61 A genotype carriers also had higher CDAI scores (p=0.19; OR=4.00; 95% CI=0.44-36.14). In addition, A+ carriers were also found to have higher requirement for anti-TNF treatment (p=0.11; OR=5.0; 95% CI=0.56-44.4). Conclusion: In this study, EGFR 497 AA genotype was found to decrease significantly in patients with UC compared to HC and CD patients. To enlighten the mechanism, further studies with larger sample groups are needed to clarify the role of the EGF (+61A/G) and EGFR R497K genes polymorphism, and development of the etiology and pathogenesis of IBD