Effect of Recepteur d'Origine Nantais expression on chemosensitivity and tumor cell behavior in colorectal cancer.

Recepteur d'Origine Nantais (RON) expression is known to induce oncogenic properties including tumor cell growth, survival, motility, angiogenesis and chemoresistance. In the present study, we evaluated whether RON affects chemosensitivity and oncogenic behavior of colorectal cancer cells and investigated its prognostic value in colorectal cancer. To evaluate the impact of RON on chemosensitivity and tumor cell behavior, we treated colorectal cancer cells with small interfering RNAs specific to RON. This was followed by flow cytometric analyses and migration, Matrigel invasion and endothelial tube formation assays. The expression of RON was investigated by immunohistochemistry in colorectal cancer tissues. TUNEL assay and immunohistochemical staining for CD34 and D2-40 were deployed to determine apoptosis, angiogenesis and lymphangiogenesis. RON knockdown enhanced 5-fluorouracil (FU)-induced apoptosis by upregulating the activities of caspases and expression of proapoptotic genes. Moreover, it enhanced 5-FU-induced cell cycle arrest by decreasing the expression of cyclins and cyclin­dependent kinases and inducing that of p21. Furthermore, RON knockdown augmented the 5-FU-induced inhibition of invasion and migration of colorectal cancer cells. The ß-catenin signaling cascade was blocked by RON knockdown upon 5-FU treatment. RON knockdown also decreased endothelial tube formation and expression of VEGF-A and HIF-1α and increased angiostatin expression. Furthermore, it inhibited lymphatic endothelial cell tube formation and the expression of VEGF-C and COX-2. RON expression was observed to be associated with age, tumor size, lymphovascular and perineural invasion, tumor stage, lymph node and distant metastasis, and poor survival rate. The mean microvessel density value of RON-positive tumors was significantly higher than that of RON-negative ones. These results indicate that RON is associated with tumor progression by inhibiting chemosensitivity and enhancing angiogenesis in colorectal cancer.

Effect of Chlorella intake on Cadmium metabolism in rats.

This study was performed to investigate the effect of chlorella on cadmium (Cd) toxicity in Cd- administered rats. Sixty male Sprague-Dawley rats (14 week-old) were blocked into 6 groups. Cadmium chloride was given at levels of 0 or 325 mg (Cd: 0, 160 ppm), and chlorella powder at levels of 0, 3 and 5%. Cadmium was accumulated in blood and tissues (liver, kidney and small intestine) in the Cd-exposed groups, while the accumulation of Cd was decreased in the Cd-exposed chlorella groups. Fecal and urinary Cd excretions were remarkably increased in Cd-exposed chlorella groups. Thus, cadmium retention ratio and absorption rate were decreased in the Cd exposed chlorella groups. Urinary and serum creatinine, and creatinine clearance were not changed in experimental animals. In addition, metallothionein (MT) synthesis in tissues was increased by Cd administration. The Cd-exposed chlorella groups indicated lower MT concentration compared to the Cd-exposed groups. Moreover, glomerular filtration rate (GFR) was not changed by dietary chlorella and Cd administration. According to the results above, this study could suggest that Cd toxicity can be alleviated by increasing Cd excretion through feces. Therefore, when exposed to Cd, chlorella is an appropriate source which counteracts heavy metal poisoning, to decrease the damage of tissues by decreasing cadmium absorption.

Intake of Chlorella vulgaris improves antioxidative capacity in rats oxidatively stressed with dietary cadmium.

BACKGROUND/AIMS: This study was designed to examine the antioxidative capacity of chlorella in rats oxidatively stressed with dietary cadmium (Cd). METHOD: Sixty male Sprague-Dawley rats (14 weeks old) were fed diets containing 0, 3 or 5% chlorella, and 0 or 160 ppm Cd for 10 weeks. Activities of antioxidant enzymes and xanthine oxidase (XO), lipid peroxide concentration and superoxide radical generation were examined in blood and liver. RESULTS: Erythrocyte superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase activities were not different among the groups. Cd treatment significantly lowered liver SOD and GPx activities; however, there were no differences induced by the chlorella content. Dietary Cd markedly increased XO activities in plasma and liver. Five percent chlorella-containing diets significantly lowered plasma XO activity, 3% chlorella-containing diets significantly lowered liver XO activity. Plasma malondialdehyde (MDA) concentration of the Cd-3% chlorella group was significantly lower than that of the Cd-0% chlorella group. Liver MDA concentration of the Cd-5% chlorella group was significantly lower than that of the Cd-0% chlorella group. Increased serum and liver superoxide radical generation by Cd was significantly attenuated by chlorella intake. CONCLUSION: Chlorella could be applied as potential substance for reducing oxidative stress, since XO activity, MDA concentration and superoxide radical generation were decreased by chlorella intake.