Effect of geldanamycin on the expression of the matrix molecules and angiogenetic factors in a gastric cancer cell line.

Angiogenesis is the formation of new blood vessels. Angiogenesis affects cancer growth and is a useful target for cancer therapeutics. The effects of geldanamycin on angiogenesis in cases of gastric cancer are poorly understood. We investigated the effects of different doses of 17-allylamino-17-demethoxygeldanamycin (17-AGG), a semi-synthetic derivative of geldanamycin, on the interactions between cellular matrix proteins and angiogenesis factors in a gastric cancer cell line. We examined cancer cells on laminin and collagen I coated surfaces to determine their response to the angiogenic effect of these matrix molecules. We also evaluated the expression levels of VEGF, MMP-9, ES and TSP-1 using ELISA. We found that application of 17-AAG to the gastric cancer cell line on culture dish plastic decreased VEGF, TSP-1, ES and MMP-9 expression, whereas of all of these proteins were increased by laminin and collagen coating. 17-AAG currently is in clinical trial phase 2 and may be a promising drug for treatment of gastric cancer.

Apoptosis of colon cancer cells under the effect of geldanamycin derivate.

AIM: The apoptotic effect of geldanamycin derivative may be important for the colorectal cancer therapy. The mechanisms of apoptosis require understanding of the behavior of colon cancer cell line Colo-205 which mimics colon adenocarcinoma. Therefore, the effect of IC50 dose of 17-allylamino-17-demethoxygeldanamycin (17-AAG) on the colon cancer cells in vitro was studied for its anti-apoptotic activity. METHOD: Apoptotic ratio of the Colo-205 cells was determined after 17-AAG application with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and apoptosis related genes. Apoptosis signal path related key mitochondrial proteins, cytochrome c, bcl-2, caspase 9 and Apaf-1 expression were examined with RT-PCR method. RESULTS: 17-AAG caused induction of cell death. Apoptotic related genes such as cytochrome-c, Apaf-1 and caspase-9 protein expressions were increased significantly (p < 0.05) and anti-apoptotic bcl-2 expression was decreased significantly (p < 0.05). Our results indicated that the application of 17-AAG on Colo-205 cells showed anticancer effect by the apoptosis due to alteration of apoptotic genes. CONCLUSION: The apoptotic effect of 17-AAG as an natural product for alternative medicine would be very important for the success and quality of life during the treatment of colon carcinoma with the combination of anticancer drugs (Tab. 1, Fig. 2, Ref. 32).

Effects of caffeic acid phenethyl ester on matrix molecules and angiogenetic and anti-angiogenetic factors in gastric cancer cells cultured on different substrates.

Migration, invasion, metastasis and angiogenesis associated with cancer depend on the surrounding microenvironment. Angiogenesis, the growth of new capillaries, is a regulator of cancer growth and a useful target for cancer therapy. We examined matrix protein interactions in a gastric cancer cell culture that was treated with different doses of caffeic acid (3,4-dihydroxycinnamic acid) phenethyl ester (CAPE). We also investigated the relations among the levels of vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), endostatin (ES) and trombospondin-1 (TSP-1). Cytotoxity of CAPE was measured using the 3-(4,5-dmethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. We examined the behavior of cells on laminin and collagen I coated surfaces in response to the angiogenic effect of these matrix molecules. We examined the protein alterations of these matrix molecules immunohistochemically and measured the levels of VEGF, MMP-9, ES and TSP-1 using the ELISA test. We showed that application of CAPE to the gastric cancer cell line on tissue culture plastic, laminin and collagen I significantly decreased the VEGF and MMP-9 protein levels. We found that TSP-1 levels were increased significantly in the gastric cancer cells after application of CAPE. The protein levels of gastric cancer cells also were increased significantly when tissue was cultured on laminin and collagen I. Application of CAPE to cells on laminin or collagen I coated surfaces significantly increased all of the proteins except ES. ES levels were increased on the collagen I covered surfaces, but the laminin surface decreased the levels of ES significantly. We demonstrated the beneficial effect of CAPE on a gastric cancer cell line including inhibition of proliferation and induction of some proteins that might be related to decreased angiogenesis.

Adipocytokine levels of colon cancer patients before and after treatment.

AIMS AND BACKGROUND: In the present study, we investigated the associations between pre- and post-treatment levels of adiponectin, ghrelin, resistin, visfatin and leptin levels in malign and benign groups. METHODS AND STUDY DESIGN: 20 malign colon carcinoma groups and 20 benign groups were included in this study. Serum levels of leptin, adiponectin, resistin, ghrelin, and visfatin were measured by Elisa kits (Milipore Corporation, Billerica, MA, USA). RESULTS: In the malign group, serum ghrelin (71.90±23.7) levels significantly decreased (p<0.05) when compared to those in the benign (88.00±16.9) group. However, serum resistin (4.92±2.2, 3.39±1.1) levels increased statistically significantly (p<0.05). In the malign group, serum visfatin (0.85±0.6, 0.83±0.5), adiponektin (60.31±23.1, 56.39±25.9) and leptin (3.08±1.4, 3.74±1.3) levels were not statistically significantly different from those in the benign group. In the malign treatment group, serum adiponectin (102.64±50.3, 66.64±27.0) levels were increased significantly (p<0.05); however, serum visfatin (1.17±0.9, 0.68±0.3), ghrelin (85.52±29.5, 82.18±18.0), leptin (5.65±2.8, 3.16±1.1), and resistin (5.96±2.8, 5.65±1.7) levels did not change significantly (p<0.05) compared to those in the respective benign treatment group. CONCLUSIONS: We showed that adipocytokines were involved in the carcinogenic process. The present results suggest that resistin and ghrelin may be important biomarkers of colon cancer. Furthermore, an in vitro study will also be necessary to evaluate the direct function of these adipocytokines in cancer cells. In addition, it will be appropriate to conduct new studies with a large number of patients at different stages (Tab. 1, Fig. 2, Ref. 24).

Thyroid hormones-mediated effects of insulin on antioxidant enzymes from diabetic rat hearts.

Free radicals, oxidative stress, and antioxidants have become commonly used terms in modern discussion of disease mechanisms. Accumulation of evidence suggests that toxic oxygen-derived reactive free radicals (superoxide, peroxide and hydroxyl radicals) play a crucial role in etiology of diabetes and its complication. Thus, it was aimed to determine the role of thyroid hormones in reversal of antioxidatant enzyme activities and lipid peroxidation alterations observed in experimentally induced diabetic rat hearts. The present study investigates the antioxidant enzyme activities such as SOD, CAT, GSH-Px and lipid peroxidation products in cardiac tissues of streptozotosin (STZ)-induced diabetic rats before and after thyroidectomy. Our results showed that CAT, GPx enzyme activities and FOX, MDA levels were increased (p<0.05) during diabetes, hypothyroidism and hypothyroidism with diabetes, which can be regulated in different percentages with treatment of insulin and various doses of thyroid hormone ((p<0.05). In conclusion, in this study, the possible contribution of thyroid hormones to the insulin effect of normalizing the induced diabetic changes in cardiac tissue and serum of rat has been seen (Tab. 5, Ref. 32).

Serum copper levels in benign and malignant thyroid diseases.

OBJECTIVE: To examine the changes in serum copper (Cu) levels in benign and malignant thyroid disease in humans. BACKGROUND: Thyroid hormones influence the metabolism of trace elements including copper. METHODS: 47 papillary thyroid cancer and 43 benign multinodular goitre patients who underwent total thyroidectomy and 37 healthy control subjects were included into this study. All of the patients and controls were females. Serum Cu levels were detected with atomic absorption spectrophotometer. RESULTS: In the papillary thyroid cancer group serum level of Cu was 131.61 ± 33.9 µg/dL before surgery and 120.81 ± 30.4 µg/dL after 20 days from surgery. In the benign group serum Cu level was 84.75 ± 12.1 µg/dL and 68.01 ± 9.4 µg/dL postoperatively.These results were compared to healthy control's value of 105.87 ± 10.68 µg/dL. In the papillary thyroid cancer group pre- and postoperative serum Cu level was significantly higher when compared to control group (p<0.05). Postoperative serum Cu level significantly decreased when compared to pre-operative level(p<0.05), in which, it was still higher than the control(p<0.05). In the benign group pre- and postoperative serum Cu level was significantly lower than in the control group (p<0.05).Postoperative serum Cu level significantly decreased when compared to pre-operative level in the benign group (p<0.05). CONCLUSION: This is a pioneer study to examine serum Cu level in benign and malignant thyroid patients compared to controls. In our small groups serum Cu levels increased in malignant thyroid patients and decreased in the benign group (Tab. 1, Ref. 18).

The effect of the sulfonylurea glyburide on glutathione-S-transferase and glucose-6-phosphate dehydrogenase in streptozotocin-induced diabetic rat liver.

Free radical-induced lipid peroxidation has been associated with numerous disease processes including diabetes mellitus. Glutathione-S-transferase (GST) catalyses the conjugation of glutathione with a variety of organic peroxides to form more water-soluble compounds. Glucose-6-phosphate dehydrogenase (G6PDH) is essential to control intracellular reductive potential by increasing glutathione intracellular levels, which in turn decrease the amount of reactive oxygen species. Glyburide decreases glucose production and enhances insulin action in liver. The aim of this study was to examine the effects of glyburide on the antioxidant enzyme activities in the liver tissue of diabetic rat. We investigated the activities of GST and G6PDH in the liver of both control and streptozotocin-induced diabetic rats. Forty male albino rats were included in this study. Liver GST and G6PDH activities decreased significantly in five-week diabetic rats (p<0.001 and p<0.001 respectively) compared to controls and glyburide therapy restored these activities (p<0.001 for GST and p<0.001 for G6PDH). Elevations of hepatic antioxidant enzymes with glyburide administration suggest that glyburide may directly alter hepatic enzyme activities.

The effects of the sulfonylurea glyburide on glutathione peroxidase, superoxide dismutase and catalase activities in the heart tissue of streptozotocin-induced diabetic rat.

Oxygen free radicals have been suggested to be a contributory factor in diabetes complications. The aim of this study was to examine the effects of glyburide on the antioxidant enzyme activities in the heart tissue of diabetic rats. We investigated the activities of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) in the hearts of both control and streptozotocin-induced diabetic rats. In the heart of diabetic rats, the activity of total superoxide dismutase decreased significantly (p < 0.005), whereas the activity of catalase and glutathione peroxidase increased to a large extent (p < 0.0001 and p = 0.05, respectively) at the end of the fourth week compared with the control group. Glyburide treatment of diabetic rats for 4 weeks corrected the changes observed in diabetic heart. In addition, blood glucose levels of untreated diabetic rats decreased following the glyburide treatment. These results demonstrate that the sulfonylurea glyburide is capable of exerting direct insulin-like effect on heart superoxide dismutase, catalase and glutathione peroxidase activities of diabetic rats in vivo.