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Tang N.-Y.,Graduate Institute of Chinese Medicine | Lai K.-C.,Chung Hwa University of Medical Technology | Chung J.-G.,China Medical UniversityTaichung404 Taiwan
Environmental Toxicology

Nonsmall cell lung carcinoma (NSCLC) is a devastating primary lung tumor resistant to conventional therapies. Bisdemethoxycurcumin (BDMC) is one of curcumin derivate from Turmeric and has been shown to induce NSCLC cell death. Although there is one report to show BDMC induced DNA double strand breaks, however, no available information to show BDMC induced DNA damage action with inhibited DNA repair protein in lung cancer cells in detail. In this study, we tested BDMC-induced DNA damage and condensation in NCI-H460 cells by using Comet assay and DAPI staining examinations, respectively and we found BDMC induced DNA damage and condension. Western blotting was used to examine the effects of BDMC on protein expression associated with DNA damage and repair and results indicated that BDMC suppressed the protein levels associated with DNA damage and repair, such as 14-3-3σ (an important checkpoint keeper of DDR), O6-methylguanine-DNA methyltransferase, DNA repair proteins breast cancer 1, early onset, mediator of DNA damage checkpoint 1 but activate phosphorylated p53 and p-H2A.X (phospho Ser140) in NCI-H460 cells. Confocal laser systems microscopy was used for examining the protein translocation and results show that BDMC increased the translocation of p-p53 and p-H2A.X (phospho Ser140) from cytosol to nuclei in NCI-H460 cells. In conclusion, BDMC induced DNA damage and condension and affect DNA repair proteins in NCI-H460 cells in vitro. © 2015 Wiley Periodicals, Inc. Source

Hsu C.-M.,Graduate Institute of Chinese Medicine | Yang M.-D.,China Medical University at Taichung | Chang W.-S.,China Medical University at Taichung | Jeng L.-B.,China Medical University at Taichung | And 7 more authors.
Anticancer Research

Background: Hepatocellular carcinoma (HCC) is a neoplasm for which the prevalence and mortality rates are very high in Taiwan. The DNA non-homologous end-joining repair gene XRCC6/Ku70 plays an important role in the repair of DNA double-strand breaks (DSBs) induced by both exogenous and endogenous DNA-damaging agents. Defects in overall DSB repair capacity can lead to genomic instability and carcinogenesis. In this study, we investigated the contribution of variant XRCC6 in relation to the risk of HCC, from the levels of DNA, RNA and protein. Materials and Methods: In this hospital-based case-control study, we collected 298 patients with HCC and 298 cancer-free controls, with frequency matched by age and gender. Firstly, the associations of XRCC6 promoter T-991C (rs5751129), promoter G-57C (rs2267437), promoter A-31G (rs132770), and intron-3 (rs132774) polymorphisms with HCC risk in this Taiwanese population were evaluated. Secondly, 30 HCC tissue samples with variant genotypes were tested to estimate the XRCC6 mRNA expression by real-time quantitative reverse transcription. Finally, the HCC tissue samples of variant genotypes were examined by immunohistochemistry and western blotting to estimate their XRCC6 protein expression levels. Results: Compared with the TT genotype, the TC and CC genotypes conferred a significantly increased risk of HCC [adjusted odds ratio (aOR)=2.43 and 3.52, 95% confidence interval (CI)=1.52-4.03 and 1.18-13.36, p=0.0003 and 0.0385, respectively]. The mRNA and protein expression levels in HCC tissues revealed statistically significantly lower XRCC6 mRNA and protein expressions in the HCC samples with TC/CC genotypes compared with those with the TT genotype (p=0.0037 and 0.0003, respectively). Conclusion: Our multi-approach findings at the DNA, RNA and protein levels suggested that XRCC6 may play an important role in HCC carcinogenesis in the Taiwanese population. © 2013 Anticancer Research. Source

Liao C.-L.,Graduate Institute of Chinese Medicine | Bau D.-T.,Chinese Institute of Clinical Medical Sciences
Environmental Toxicology

Melanoma cancer is one of the major causes of death in humans worldwide. Triptolide is one of the active components of Tripterygium wilfordii Hook F, and has biological activities including induced cell cycle arrest and induction of apoptosis but its antimetastatic effects on murine melanoma cells have not yet been elucidated. Herein, we investigated the effect of triptolide on the inhibition of migration and invasion and possible associated signal pathways in B16F10 murine melanoma cancer cells. Wound healing assay and Matrigel Cell Migration Assay and Invasion System demonstrated that triptolide marked inhibiting the migration and invasion of B16F10 cells. Gelatin zymography assay demonstrated that triptolide significantly inhibited the activities of matrix metalloproteinases-2 (MMP-2). Western blotting showed that triptolide markedly reduced CXCR4, SOS1, GRB2, p-ERK, FAK, p-AKT, Rho A, p-JNK, NF-κB, MMP-9, and MMP-2 but increased PI3K and p-p38 and COX2 after compared to the untreated (control) cells. Real time PCR indicated that triptolide inhibited the gene expression of MMP-2, FAK, ROCK-1, and NF-κB but did not significantly affect TIMP-1 and -2 gene expression in B16F10 cells in vitro. EMSA assay also showed that triptolide inhibited NF-κB DNA binding in a dose-dependent manner. Confocal laser microscopy examination also confirmed that triptolide inhibited the expression of NF-κB in B16F10 cells. Taken together, we suggest that triptolide inhibited B16F10 cell migration and invasion via the inhibition of NF-κB expression then led to suppress MMP-2 and -9 expressions. © 2015 Wiley Periodicals, Inc. Source

Tang N.-Y.,Graduate Institute of Chinese Medicine | Liao C.-L.,Graduate Institute of Chinese Medicine | Lu H.-F.,Fu Jen Catholic UniversityTaipei Taiwan
Environmental Toxicology

Curcuminoids are the major natural phenolic compounds found in the rhizome of many Curcuma species. Curcuminoids consist of a mixture of curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC). Although numerous studies have shown that curcumin induced cell apoptosis in many human cancer cells, however, mechanisms of BDMC-inhibited cell growth and -induced apoptosis in human lung cancer cells still remain unclear. Herein, we investigated the effect of BDMC on the cell death via the cell cycle arrest and induction of apoptosis in NCI H460 human lung cancer cells. Flow cytometry assay was used to measure viable cells, cell cycle distribution, the productions of reactive oxygen species (ROS) and Ca2+, mitochondrial membrane potential (ΔΨm) and caspase-3, -8 and -9 activity. DNA damage and condension were assayed by Comet assay and DAPI staining, respectively. Western blotting was used to measure the changes of cell cycle and apoptosis associated protein expressions. Results indicated that BDMC significantly induced cell death through induced S phase arrest and induced apoptosis. Moreover, DMC induced DNA damage and condension, increased ROS and Ca2+ productions and decreased the levels of ΔΨm and promoted activities caspase-3, -8, and -9. Western blotting results showed that BDMC inhibited Cdc25A, cyclin A and E for causing S phase arrest, furthermore, promoted the expression of AIF, Endo G and PARP and the levels of Fas ligand (Fas L) and Fas were also up-regulated. Results also indicated that BDMC increased ER stress associated protein expression such as GRP78, GADD153, IRE1α, IRE1β, ATF-6α, ATF-6β, and caspase-4. Taken together, we suggest that BDMC induced cell apoptosis through multiple signal pathways such as extrinsic, intrinsic and ES tress pathway. © 2015 Wiley Periodicals, Inc. Source

Liao C.-L.,Graduate Institute of Chinese Medicine
Environmental Toxicology

Various sedative agents, including dexmedetomidine (dex), induce immunosuppression, and enhance infection progression. However, there was no information on how anesthetic affects local and systemic cellular immune function. We conducted this study to examine the impact of dex on the differentiation and function of immune cells at site of inflammation and in peripheral blood during endotoxemia of mice. In BALB/c mice with and without endotoxemia, we evaluated the influence of two dosages of 5 and 50 mcg/kg/h intravenous dex on immune cells: including number of T cells (CD3), B cells (CD19), natural killer cells (CD8a), monocytes (CD11b), and macrophages (Mac-3) in peripheral blood, the activities of macrophages in peripheral blood and in peritoneal lavage, and proliferation of B and T cells and of natural killer cells activity in the spleen. Endotoxemia increased the number of CD3 T cells, CD 19 B cells and macrophages in the peripheral blood, augmented macrophage activity in the peritoneum, and increased T cell proliferation and natural killer cell activity in the spleen. Further administration of 5 mcg/kg/h dex attenuated systemic increase in number of T cells, B cells, and macrophages during endotoxemia and 50 mcg/kg/h dex significantly attenuated the increase in activity of macrophages in the peripheral blood during endotoxemia. In the peritoneum, however, 5 mcg/kg/h dex preserved and 50 mcg/kg/h dexmedetomidine enhanced the activity of macrophages during endotoxemia. Increased in proliferation of T cells in spleen during endotoxemia was attenuated by both doses of dex. Last, 50 mcg/kg/h dex enhanced natural killer cells activity during endotoxemia. While preserving the effects of endotoxemia on macrophage's activity in the infection site and natural killer cell's activity in the spleen, dex decreased systemic fulminant immune reaction in endotoxemia, by attenuating the augmented response in the number of T cells, B cells and macrophages, activity of macrophages in the peripheral blood, and proliferation of T cells in spleen during endotoxemia. © 2014 Wiley Periodicals, Inc. Source

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