Embelin induces apoptosis of human gastric carcinoma through inhibition of p38 MAPK and NF-κB signaling pathways.

Embelin is a small-molecule inhibitor of X­linked inhibitor of apoptosis protein (XIAP), and it induces apoptosis in tumor cells via the inhibition of XIAP. The aim of the present study was to investigate the anticancer effect of embelin on human gastric carcinoma cells and the mechanisms underlying this effect. Cell proliferation of SGC7901 human gastric carcinoma cells was measured using MTT assay, following treatment with embelin (5, 10 and 15 µM) on days 1, 3 and 5. Caspase­3 and nuclear factor (NF)­κB p65 activation in SGC7901 cells were assessed using commercial kits. Cellular and nuclear apoptosis were analyzed with an Annexin V­FITC/PI Apoptosis Detection kit and DAPI staining assay, respectively. Phospho (p)­p38 mitogen­activated protein kinase (MAPK), p­inhibitor of NF­κB (p­IκBα) and p­IκB kinase α/ß (p­IKKα/ß) protein expression levels were analyzed with western blot assay. In the present study, treatment with embelin decreased cell proliferation, induced caspase­3 activation and suppressed NF­κB p65 activation in SGC7901 cells. Furthermore, embelin administration reduced p­IκBα and p­IKKα/ß protein expression levels. In conclusion, embelin induces cell apoptosis in human gastric carcinoma through activation of p38 MAPK and inhibition of the NF­κB signaling pathways. It was further suggested that embelin may be used as a potential drug for the treatment of gastric carcinoma.

Hyperhomocysteinemia and related genetic polymorphisms correlate with ulcerative colitis in Chinese Han population in Central China [corrected].

Increased levels of homocysteine are found systemically and in intestinal mucosa of patients with inflammatory bowel disease, and, specifically, in ulcerative colitis (UC). However, there are controversial reports regarding the factors contributing to increased levels of homocysteine in UC. Furthermore, little information is available regarding the relationship between hyperhomocysteinemia (HHcy), vitamin status, and genetic polymorphisms of homocysteine-related enzymes in these patients. This study examined four functional polymorphisms linked to homocysteine metabolism (MTHFR C677T and A1298C, MTR A2756G and MTRR A66G), and evaluated plasma levels of homocysteine, folate, and vitamin B(12) in 310 consecutive patients with UC and 936 age- and sex-matched healthy controls from southeast China. The variant allele and genotypic frequencies in MTHFR A1298C, MTR A2756G and MTRR A66G genes were significantly higher in patients with UC compared to healthy controls. Further, HHcy and low levels of folate and vitamin B(12) were more frequent in patients with UC. The MTR 2756G allele, extent of the disease, and gender were the independent determinants of HHcy in these patients. These findings suggest that genetic and nutritional factors have a synergetic effect on HHcy in patients with UC. In conclusion, our data highlight a prevention strategy for moderation of HHcy and supplementation with folate and vitamine B(12) in patients with UC from Southeast China.