Protective Effects of Tetrahydrocurcumin and Curcumin against Doxorubicin and Cadmium-Induced Cytotoxicity in Chang Liver Cells

Purpose: To investigate the cytoprotective effect of tetrahydrocurcumin, (THC) and curcumin (CUR) on cytotoxicity induced by doxorubicin and cadmium in Chang liver cells.Methods: Cytotoxicity was determined by sulforhodamine B assay. The expression of nuclear  factorerythroid- 2-related factor 2 (Nrf2) Nrf2 regulated  cytoprotecetive enzymes, glutamylcysteine ligase catalytic subunit (GCLC) and NADP (H): quinone oxidoreductase1 (NQO1) was determined by Western blot  analysis. Nuclear translocation of Nrf-2 was analyzed by immunofluorescence method. The level of superoxide formation was assayed by chemiluminescence  method.Results: Treatment with THC or CUR significantly induced GCLC and NQO1 expression and the nuclear translocation of Nrf2. Exposure to doxorubicin (DOX) or Cd for 24 h induced cell death of about 50 %.  However, pre-treatment with THC or CUR (1 or 6 μM) for 24 h significantly increased cell survival to 80 or 90 %,  respectively (p < 0.05). Similar pre-treatment with THC or CUR significantly protected against Cd-induced cell death by a level of 80 and 85 %, respectively (p < 0.05). The cytoprotective effect of these compounds was associated with suppressed DOX- and Cd-induced superoxide formation and induction of GCLC and NQO1 expression.Conclusions: THC mediates its effects by activation of Nrf2 and its regulated enzymes, GCLC and NQO1. Induction of GCLC, NQO1 protein expression and suppression of superoxide are associated with the cytoprotective effect.Keywords: Chang hepatocyte, Curcumin, Tetrahydrocurcumin, Cytoprotection, Doxorubicin, Cadmiu

Association of arterial stiffness with single nucleotide polymorphism rs1333049 and metabolic risk factors

The electronic version of this article is the complete one and can be found online at: http://www.cardiab.com/content/12/1/93. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.BACKGROUND: Increased arterial stiffness is a cardiovascular outcome of metabolic syndrome (MetS). The chromosome 9p21 locus has been identified as a major locus for risk of coronary artery disease (CAD). The single nucleotide polymorphism (SNP), rs1333049 on chromosome 9p21.3 has been strongly associated with CAD and myocardial infarction. Increased arterial stiffness could be the link between the 9p21 polymorphism and increased cardiovascular risk. Since the impact of a genetic polymorphism on arterial stiffness especially in Asian populations has not been well defined, we aimed to investigate the association of arterial stiffness with rs 1333049 variant on chromosome 9p21.3 in Thai subjects with and without MetS risk factors. METHODS: A total of 208 Thai subjects, aged 35-75 years, 135 with and 73 without MetS, according to IDF and NCEP-ATPIII criteria, were included in this study. Aortic-femoral pulse wave velocity (afPWV), brachial-ankle pulse wave velocity (baPWV) and aortic ankle pulse wave velocity (aaPWV) were measured and used as markers of arterial stiffness. The chromosome 9p21.3 locus, represented by the rs 1333049 variant and blood biochemistry were evaluated. RESULTS: Arterial stiffness was elevated in subjects with MetS when compared with nonMetS subjects. PWV, especially afPWV increased progressively with increasing number of MetS risk factors (r = 0.322, P <0.001). We also found that the frequency distribution of the rs1333049 genotypes is significantly associated with the afPWV (P <0.05). In multivariate analyses, there was an association between homozygous C allele and afPWV (Odds ratio (OR), 8.16; 95% confidence interval (CI), 1.91 to 34.90; P = 0.005), while the GC genotype was not related to afPWV (OR, 1.79; 95% CI, 0.84 to 3.77; P = 0.129) when compared with the GG genotype. CONCLUSIONS: Our findings demonstrate for the first time that arterial stiffness is associated with genetic polymorphism in 9p21 and metabolic risk factors in a Thai population

The green tea catechin epigallocatechin gallate induces cell cycle arrest and shows potential synergism with cisplatin in biliary tract cancer cells

BACKGROUND: The green tea catechin epigallocatechin gallate (EGCG) was shown to effectively inhibit tumor growth in various types of cancer including biliary tract cancer (BTC). For most BTC patients only palliative therapy is possible, leading to a median survival of about one year. Chemoresistance is a major problem that contributes to the high mortality rates of BTC. The aim of this study was to investigate the cytotoxic effect of EGCG alone or in combination with cisplatin on eight BTC cell lines and to investigate the cellular anti-cancer mechanisms of EGCG. METHODS: The effect of EGCG treatment alone or in combination with the standard chemotherapeutic cisplatin on cell viability was analyzed in eight BTC cell lines. Additionally, we analyzed the effects of EGCG on caspase activity, cell cycle distribution and gene expression in the BTC cell line TFK-1. RESULTS: EGCG significantly reduced cell viability in all eight BTC cell lines (p < 0.05 or p < 0.01, respectively, for most cell lines and EGCG concentrations > 5 μM). Combined EGCG and cisplatin treatment showed a synergistic cytotoxic effect in five cell lines and an antagonistic effect in two cell lines. Furthermore, EGCG reduced the mRNA levels of various cell cycle-related genes, while increasing the expression of the cell cycle inhibitor p21 and the apoptosis-related death receptor 5 (p < 0.05). This observation was accompanied by an increase in caspase activity and cells in the sub-G1 phase of the cell cycle, indicating induction of apoptosis. EGCG also induced a down-regulation of expression of stem cell-related genes and genes that are associated with an aggressive clinical character of the tumor, such as cd133 and abcg2. CONCLUSIONS: EGCG shows various anti-cancer effects in BTC cell lines and might therefore be a potential anticancer drug for future studies in BTC. Additionally, EGCG displays a synergistic cytotoxic effect with cisplatin in most tested BTC cell lines. [Figure: see text