alpha-Mangostin, a novel dietary xanthone, suppresses TPA-mediated MMP-2 and MMP-9 expressions through the ERK signaling pathway in MCF-7 human breast adenocarcinoma cells.

This study first investigates the anti-metastatic effect of alpha-mangostin on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) expressions in human breast adenocarcinoma cells, MCF-7. First, the result demonstrated alpha-mangostin could inhibit TPA-induced abilities of the adhesion, invasion, and migration by cell-matrix adhesion assay and Boyden chamber assay. Data also showed alpha-mangostin could inhibit the activation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) involved in the downregulation the enzyme activities, protein, and messenger RNA levels of MMP-2 and MMP-9 induced by TPA. Next, alpha-mangostin also strongly inhibited TPA-induced degradation of inhibitor of kappaBalpha (IkappaBalpha) and the nuclear levels of nuclear factor kappa B (NF-kappaB), c-Fos, and c-Jun. Also, a dose-dependent inhibition on the binding abilities of NF-kappaB and activator protein-1 (AP-1) by alpha-mangostin treatment was further observed. Further, the treatment of specific inhibitor for ERK (U0126) to MCF-7 cells could inhibit TPA-induced MMP-2 and MMP-9 expressions along with an inhibition on cell invasion and migration. Presented data reveal that alpha-mangostin is a novel, effective, antimetastatic agent that functions by downregulating MMP-2 and MMP-9 gene expressions.

Plumbagin inhibits invasion and migration of liver cancer HepG2 cells by decreasing productions of matrix metalloproteinase-2 and urokinase- plasminogen activator.

AIM: To investigate the inhibitory effects of plumbagin (5-hydroxy-2 methyl-1,4-naphthoquinone) on the invasion and migration and its correlation with matrix metalloproteinase-2 (MMP-2) and urokinase-plasminogen activator (u-PA) in liver cancer HepG2 cells under non-cytotoxic concentrations. METHODS: The cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The adhesion, migration and invasion were measured by cell-matrix adhesion assay and Boyden chamber assay. The MMP-2 and u-PA activities were estimated by gelatin and casein-plasminogen zymography. The mRNA and protein levels of MMP-2, u-PA, urokinase-plasminogen activator receptor (u-PAR), tissue inhibitor of metalloproteinase-2 (TIMP-2), plasminogen activator inhibitor-1 (PAI-1), nuclear factor kappa B (NF-kappaB), c-Fos and c-Jun were evaluated by semi-quantitative reverse transcription polymerase chain reaction and western blotting. Also, the binding abilities of NF-kappaB and activator protein-1 (AP-1) were analyzed by electrophoretic mobility shift assay (EMSA). RESULTS: In this study, plumbagin had exhibited an inhibitory effect on the abilities of adhesion, migration and invasion. The results from zymography showed plumbagin treatment may decrease the activities of MMP-2 and u-PA. Further, the mRNA and protein levels of MMP-2, u-PA and u-PAR were significantly reduced, while TIMP-2 and PAI-1 were elevated by plumbagin treatment. Next, plumbagin significantly decreased the nuclear levels of NF-kappaB, c-Fos and c-Jun. Also, treating HepG2 cells with plumbagin leads to dose-dependent inhibition on the binding abilities of NF-kappaB and AP-1. CONCLUSION: We demonstrated the inhibitory effects of plumbagin on the invasion, migration and adhesion of HepG2 cells, while plumbagin treatment may decrease the expressions of MMP-2 and u-PA and enhance the expressions of TIMP-2 and PAI-1.

Increased risk of viral hepatitis in Taiwanese male conscriptees with tattoos.

A number of previous literature reviews and research studies have found a correlation between viral hepatitis infections and tattoos. The 1897 subjects of the current study were young adult male military recruits in southern Taiwan (476 with tattoos and 1421 without tattoos) who underwent induction physical examinations before conscription. During the examination, blood samples were collected to screen for hepatitis B surface antigen, antibodies to hepatitis C virus (anti-hepatitis B HCV), syphilis, and human immunodeficiency virus. Approximately 25.1% had tattoos, 11.3% were positive for HBV surface antigen, 2.5% were positive for HCV antibody, and 2.1% were positive for HCV RNA. The odds ratios for positive hepatitis B virus and HCV infection status were 1.38 (95% confidence interval, 0.98-1.93) and 5.00 (95% confidence interval, 1.83-13.67), respectively, for those with tattoos, compared with those with no tattoos. All conscriptees were seronegative for syphilis and human immunodeficiency virus.