Effects of Mutations of 3 Amino Acids on Hepatocellular Carcinoma: A Systematic Review and Meta-analysis.

In recent years, over 1000 reports have been published on the association between hepatic diseases and gene mutations which may result in pathogenic amino acids. Most of the studies focus on the hepatocellular carcinoma (HCC). The aim was to systematically examine the published literature on the association between the mutations of arginine, serine, and threonine and hepatic diseases, particularly HCC. The Biosciences information service database was systematically searched before July 10, 2012. Of the initially selected 471 publications, 112 articles were included in this study. Meta-analyses were conducted for 3 amino acids. Risk ratios were used to analyze the association between amino acids and liver diseases. We analyze the literature on the association between gene mutations and hepatic diseases, especially in patients with HCC. Full-text articles were analyzed by 4 independent researchers. Some amino acid mutations were found only in people with liver diseases--not in the general population. Arginine and threonine mutations occurred more frequently in patients with hepatic diseases, compared to the normal population. There is a statistically significant association between arginine mutations and the risk of HCC and serine mutations and the risk of HCC.

Suppression of human breast cancer cell metastasis by coptisine in vitro.

BACKGROUND: Coptisine, an isoquinoline alkaloid extracted from Coptidis rhizoma, has many biological activities such as antidiabetic, antimicrobial and antiviral actions. However, whether coptisine exerts anti-cancer metastasis effects remains unknown. MATERIALS AND METHODS: Effects of coptisine on highly metastatic human breast cancer cell MDA-MB-231 proliferation were evaluated by trypan blue assay and on cell adhesion, migration and invasion by gelatin adhesion, wound-healing and matrigel invasion chamber assays, respectively. Expression of two matrix metalloproteinases (MMPs), MMP-9, MMP-2 and their specific inhibitors tissue inhibitor of metalloproteinase 1 (TIMP-1) and tissue inhibitor of metalloproteinase 2 (TIMP-2) were analyzed by RT-PCR. RESULTS: Coptisine obviously inhibited adhesion to an ECM-coated substrate, wound healing migration, and invasion through the matrigel in MDA-MB-231 breast cancer cells. RT-PCR revealed that coptisine reduced the expression of the ECM degradation-associated gene MMP-9 at the mRNA level, and the expression of TIMP-1 was up-regulated in MDA-MB-231 cells, while the expression of MMP-2 and its specific inhibitor TIMP-2 was not affected. CONCLUSIONS: Taken together, our data showed that coptisine suppressed adhesion, migration and invasion of MDA-MB-231 breast cancer cells in vitro, the down-regulation of MMP-9 in combination with the increase of TIMP-1 possibly contributing to the anti-metastatic function. Coptisine might be a potential drug candidate for breast cancer therapy.