• Journal of Life Science
• /
• v.15 no.3 s.70
• /
• pp.323-331
• /
• 2005

The objective of the present study was to investigate the effect of $\beta-lapachone$, a quinone obtained from the bark of the lapacho tree (Tabebuia avellanedae) in South America, on the cell growth of human hepatoma (HepG2) and bladder (T24) carcinoma cells. Exposure of cancer cells to $\beta-lapachone$ resulted in growth inhibition, morphological changes and apoptosis in a concentration-dependent manner, which could be proved by MTT assay and flow cytometry analysis. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analyses revealed that $\beta-lapachone$ did not affect the levels of tumor suppressor p53 and cyclin-dependent kinase (Cdk) inhibitor p21 (WAFl/CIPl) expression. However, the transcriptional factor Sp-l and proliferating cell nuclear antigen (PCNA) protein levels were significantly down-regulated by $\beta-lapachone$ in both cell lines. Moreover, $\beta-lapachone$ treatment caused a dose-dependent inhibition of the expression of telomere regulatory gene products such as human telomere reverse transcriptase (hTERT) and telomerase-associated protein-l (TEP-l). Taken together, these findings suggest that $\beta-lapachone$-induced inhibition of human hepatoma and bladder carcinoma cell proliferation is associated with the induction of apoptotic cell death via modulation of several major growth regulatory gene products, and provide important new insights into the additional mechanisms of the anti-cancer activity of $\beta-lapachone$.

• Molecules and Cells
• /
• v.37 no.10
• /
• pp.759-765
• /
• 2014

N-myc downstream-regulated gene 2 (NDRG2), which is known to have tumor suppressor functions, is frequently down-regulated in breast cancers and potentially involved in preventing the migration and invasion of malignant tumor cells. In the present study, we examined the inhibitory effects of NDRG2 overexpression, specifically focusing on the role of cyclooxygenase-2 (COX-2) in the migration of breast cancer cells. NDRG2 overexpression in MDA-MB-231 cells inhibited the expression of the COX-2 mRNA and protein, the transcriptional activity of COX-2, and prostaglandin $E_2$ ($PGE_2$) production, which were induced by a treatment with phorbol-12-myristate-13-acetate (PMA). Nuclear transcription factor-${\kappa}B$ (NF-${\kappa}B$) signaling attenuated by NDRG2 expression resulted in a decrease in PMA-induced COX-2 expression. Interestingly, the inhibition of COX-2 strongly suppressed PMA-stimulated migration and invasion in MDA-MB-231-NDRG2 cells. Moreover, siRNA-mediated knockdown of NDRG2 in MCF7 cells increased the COX-2 mRNA and protein expression levels and the PMA-induced COX-2 expression levels. Consistent with these results, the migration and invasion of MCF7 cells treated with NDRG2 siRNA were significantly enhanced following treatment with PMA. Taken together, our data show that the inhibition of NF-${\kappa}B$ signaling by NDRG2 expression is able to suppress cell migration and invasion through the down-regulation of COX-2 expression.

• Microbiology and Biotechnology Letters
• /
• v.44 no.2
• /
• pp.117-123
• /
• 2016

In this study, to evaluate the anti-oxidative and anti-inflammatory effects of Carpinus pubescens Burkill ethanol extract (CPEE), we performed the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, reactive oxygen species (ROS) inhibition, and nitric oxide (NO) scavenging assays and an analysis of the related protein expressions. CPEE showed high DPPH radical scavenging activity and effectively increased ROS inhibition activity dose-dependently. Furthermore, CPEE induced the expression of the anti-oxidative enzyme heme oxygenase 1 and its upstream transcription factor, nuclear factor-E2-related factor 2, in RAW 264.7 cells. CPEE was associated with a reduction in NO production, which was induced by lipopolysaccharide treatment in a dose-dependent manner. The expression of inducible nitric oxide synthase (iNOS), an upstream regulator of NO production, was also inhibited. Taken together, these results suggest that CPEE has anti-oxidative and anti-inflammatory activities and could be useful as a potential anti-oxidant and antiinflammatory agent.

• IMMUNE NETWORK
• /
• v.12 no.5
• /
• pp.181-188
• /
• 2012

Dioscoreae Rhizome (DR) has been used in traditional medicine to treat numerous diseases and is reported to have anti-diabetes and anti-tumor activities. To identify a bioactive traditional medicine with anti-inflammatory activity of a water extract of DR (EDR), we determined the mRNA and protein levels of proinflammatory cytokines in macrophages through RT-PCR and western blot analysis and performed a FACS analysis for measuring surface molecules. EDR dose-dependently decreased the production of NO and pro-inflammatory cytokines such as IL-$1{\beta}$, IL-6, TNF-${\alpha}$, and $PGE_2$, as well as mRNA levels of iNOS, COX-2, and pro-inflammatory cytokines, as determined by western blot and RT-PCR analysis, respectively. The expression of co-stimulatory molecules such as B7-1 and B7-2 was also reduced by EDR. Furthermore, activation of the nuclear transcription factor, NF-${\kappa}B$, but not that of IL-4 and IL-10, in macrophages was inhibited by EDR. These results show that EDR decreased pro-inflammatory cytokines via inhibition of NF-${\kappa}B$-dependent inflammatory protein level, suggesting that EDR could be a useful immunomodulatory agent for treating immunological diseases.

• BMB Reports
• /
• v.44 no.8
• /
• pp.547-552
• /
• 2011

MED19 is a member of the Mediator that plays a key role in the activation and repression of signal transduction or the regulation of transcription in carcinomas. To tested the functional role of MED19 in human prostate cancer, we downregulated MED19 expression in prostate cancer cells (PC-3 and DU145) by lentivirus-mediated short hairpin (shRNA), and analyzed the effect of inhibition of MED19 on prostate cancer cell proliferation and tumorigenesis. The in vitro prostate cancer cell proliferation, colony formation, and in vivo tumor growth in nude mice xenografts was significantly reduced after the downregulation of MED19. Knockdown of MED19 caused S-phase arrest and induced apoptosis via modulation of Bid and Caspase 7. It was suggested that MED19 serves as a novel proliferation regulator that promotes growth of prostate cancer cells.

• Toxicological Research
• /
• v.34 no.1
• /
• pp.13-21
• /
• 2018

Anthocyanins are naturally occurring water-soluble polyphenolic pigments in plants that have been shown to protect against cardiovascular diseases, and certain cancers, as well as other chronic human disorders. However, the anti-obesity effects of anthocyanins are not fully understood. In this study, we investigated the effects of anthocyanins isolated from the fruit of Vitis coignetiae Pulliat on the adipogenesis of 3T3-L1 preadipocytes. Our data indicated that anthocyanins attenuated the terminal differentiation of 3T3-L1 preadipocytes, as confirmed by a decrease in the number of lipid droplets, lipid content, and triglyceride production. During this process, anthocyanins effectively enhanced the activation of the AMP-activated protein kinase (AMPK); however, this phenomenon was inhibited by the co-treatment of compound C, an inhibitor of AMPK. Anthocyanins also inhibited the expression of adipogenic transcription factors, including peroxisome proliferator-activated receptor-${\gamma}$, CCAAT/enhancer-binding protein a and b, and sterol regulatory element-binding protein-1c. In addition, anthocyanins were found to potently inhibit the expression of adipocyte-specific genes, including adipocyte fatty acid-binding protein, leptin, and fatty acid synthase. These results indicate that anthocyanins have potent anti-obesity effects due to the inhibition of adipocyte differentiation and adipogenesis, and thus may have applications as a potential source for an anti-obesity functional food agent.

• Journal of Microbiology and Biotechnology
• /
• v.11 no.6
• /
• pp.1061-1065
• /
• 2001

The antibacterial effects of water extracts of Scutellariate Radix (a dried root of Scutellaria baicalensis GEORGI) and its major flavonoid components, Baicalin and Baicalein, on Salmonella typhimurium, a representative enteric pathogen, were studied. Through a Kriby-Bauer disc analysis, the growth-inhibition activity of Scutellariae Radix against. S. typhimurium was found to be compatible with commercial antibiotics, such as ampicillin, chloramphenicol, and streptomycin. In contrast, the growth of a nonpathogenic E. coli strain was unaffercted by Scutellariae Radix. To examine the effect of polyphosphate kinase (ppk), a putative virulence factor, on the antibacterial activity of Scutellariae Radix, the growth profile of a ppk mutant of S. typhimurium was investigated in a tryptic soy broth containing different concentrations of water extracts of Scutellariae Radix. The ppk mutant was able to grow in 6 mg/ml of water extracts of Scutellariae Radix, whereas in 6 mg/ml of water extracts of Scutellariae Radix, whereas the wild-type could not, implying that the inactivation of ppk made S. typhimurium more resistant to the antibacterial activity of Scutellariae Radix. No enhanced resistance was observed in a ppk mutant of S. typhimurium complemented with a ppk expression vector. The attenuation of the virulence by ppk inactivation was also observed in a virulence assay using BLAB/c mice. Neither Baicalin nor Baicalein exhibited any growth-inhibition activity against S. typhimurium. The water extracts of Scutellariae Radix stimulated the transcription of ppk, especially in the early growth-stage of S. typhimurium.

• Nutrition Research and Practice
• /
• v.3 no.2
• /
• pp.84-88
• /
• 2009

In our previous study, we have shown that berberine has both anti-adipogenic and anti-inflammatory effects on 3T3-L1 adipocytes, and the anti-adipogenic effect is due to the down-regulation of adipogenic enzymes and transcription factors. Here we focused more on anti-inflammatory effect of berberine using real time RT-PCR and found it changes expressions of adipokines. We hypothesized that anti-adipogenicity of berberine mediates anti-inflammtory effect and explored leptin as a candidate mediator of this signaling. We studied this hypothesis by western blot analysis, but our results showed that berberine has no effect on the phosphorylations of STAT-3 and ERK which have important roles on leptin signaling. These results led us to conclude that the anti-inflammatory effect of berberine is not mediated by the inhibition of leptin signal transduction. Moreover, we have found that berberine down-regulates NF-${\kappa}B$ signaling, one of the inflammation-related signaling pathway, through western blot analysis. Taken together, the anti-inflammatory effect of berberine is not mediated by leptin, and berberine induces anti-inflammatory effect independent of leptin signaling.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.16
• /
• pp.6581-6586
• /
• 2014

Background: The istone deacetylase (HDAC) inhibitor trichostatin A (TSA) is known to mediate the regulation of gene expression and antiproliferation activity in cancer cells. Kr$\ddot{u}$ppel-like factor 4 (klf4) is a zinc finger-containing transcription factor of the SP/KLF family, that is expressed in a variety of tissues and regulates cell proliferation, differentiation, tumorigenesis, and apoptosis. It may either either function as a tumor suppressor or an oncogene depending on genetic context of tumors. Aims: In this study, we tested the possibility that TSA may increase klf4 expression and cancer cell growth inhibition and apoptosis in SKOV-3 and A549 cells. Materials and Methods: The cytotoxicity of TSA was determined using the MTT assay test, while klf4 gene expression was assessed by real time PCR andto ability of TSA to induce apoptosis using a Vybrant Apoptosis Assay kit. Results: Our results showed that TSA exerted dose and time dependent cytotoxicity effect on SKOV-3 and A549 cells. Moreover TSA up-regulated klf4 expression. Flow cytometric analysis demonstrated that apoptosis was increased after TSA treatment. Conclusions: Taken together, this study showed that TSA increased klf4 expression in SKOV3 and A549 cell lines, consequently, klf4 may played a tumor-suppressor role by increasing both cell growth inhibition and apoptosis. This study sheds light on the details of molecular mechanisms of HDACI-induced cell cycle arrest and apoptosis.

• Nutrition Research and Practice
• /
• v.9 no.6
• /
• pp.592-598
• /
• 2015

BACKGROUND/OBJECTIVES: Increased mass of adipose tissue in obese persons is caused by excessive adipogenesis, which is elaborately controlled by an array of transcription factors. Inhibition of adipogenesis by diverse plant-derived substances has been explored. The aim of the current study was to examine the effects of the aqueous methanol extract of laver (Porphyra yezoensis) on adipogenesis and apoptosis in 3T3-L1 adipocytes and to investigate the mechanism underlying the effect of the laver extract. MATERIALS/METHODS: 3T3-L1 cells were treated with various concentrations of laver extract in differentiation medium. Lipid accumulation, expression of adipogenic proteins, including CCAAT enhancer-binding protein ${\alpha}$, peroxisome proliferator-activated receptor ${\gamma}$, fatty acid binding protein 4, and fatty acid synthase, cell viability, apoptosis, and the total content and the ratio of reduced to oxidized forms of glutathione (GSH/GSSG) were analyzed. RESULTS: Treatment with laver extract resulted in a significant decrease in lipid accumulation in 3T3-L1 adipocytes, which showed correlation with a reduction in expression of adipogenic proteins. Treatment with laver extract also resulted in a decrease in the viability of preadipocytes and an increase in the apoptosis of mature adipocytes. Treatment with laver extract led to exacerbated depletion of cellular glutathione and abolished the transient increase in GSH/GSSG ratio during adipogenesis in 3T3-L1 adipocytes. CONCLUSION: Results of our study demonstrated that treatment with the laver extract caused inhibition of adipogenesis, a decrease in proliferation of preadipocytes, and an increase in the apoptosis of mature adipocytes. It appears that these effects were caused by increasing oxidative stress, as demonstrated by the depletion and oxidation of the cellular glutathione pool in the extract-treated adipocytes. Our results suggest that a prooxidant role of laver extract is associated with its antiadipogenic and proapoptotic effects.