• Toxicological Research
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• v.31 no.4
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• pp.339-345
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• 2015

CYP1A1 is a phase I xenobiotic-metabolizing enzyme whose expression is mainly driven by AhR. Endosulfan is an organochlorine pesticide used agriculturally for a wide range of crops. In this study, we investigated the effect of endosulfan on CYP1A1 expression and regulation. Endosulfan significantly increased CYP1A1 enzyme activity as well as mRNA and protein levels. In addition, endosulfan markedly induced XRE transcriptional activity. CH-223191, an AhR antagonist, blocked the endosulfan-induced increase in CYP1A1 mRNA and protein expression. Moreover, endosulfan did not induce CYP1A1 gene expression in AhR-deficient mutant cells. Furthermore, endosulfan enhanced the phosphorylation of calcium calmodulin (CaM)-dependent protein kinase (CaMK) and protein kinase C (PKC). In conclusion, endosulfan-induced up-regulation of CYP1A1 is associated with AhR activation, which may be mediated by PKC-dependent pathways.

• Journal of Microbiology and Biotechnology
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• v.16 no.11
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• pp.1819-1825
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• 2006

Four naphthalene-degrading bacteria (Pseudomonas sp. strains O1, W1, As1, and G1) were isolated feom pollutant-contaminated sites. Examination of their substrate utilization and analyses of key naphthalene-catabolic regulatory genes revealed that the pathway and regulation of naphthalene-degradation in all four strains resemble those of NAH7 from P. putida G7. Superoxide anion production, superoxide dismutase activity, and catalase activity during their growth on naphthalene-amended medium increased significantly, compared with those with glucose-amended medium. Addition of ascorbate, an antioxidant, or ferrous iron ($Fe^{2+}$) increased the growth rates of all tested microorganisms on naphthalene. Northern blot and HPLC analyses showed that both nahA gene expression and naphthalene degradation increased under those conditions. Our data suggest that naphthalene degradation can impose severe oxidative stress, and defenses against oxidative stress would play an important role in the metabolism of naphthalene.

• Preventive Nutrition and Food Science
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• v.22 no.1
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• pp.50-55
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• 2017

Raphanus sativus L. (RS) is a cruciferous vegetable that is widely consumed in Korea. The anticancer activity of leaves of RS (RSL) extract has been investigated; however, no studies focused on its anti-inflammatory effects. Therefore, the aim of the current study was to evaluate the anti-inflammatory effects of RSL extract. In brief, RSL powder was fractionated into n-hexane, chloroform, ethyl acetate, n-butanol, and water-soluble fractions. Lipopolysaccharide (LPS)-stimulated RAW264.7 cells were treated with each fraction for initial screening. It was found that the chloroform fraction significantly inhibited nitric oxide release in LPS-stimulated RAW264.7 cells with a half maximal inhibitory concentration value of $196{\mu}g/mL$. In addition, the mRNA and protein expression levels of inducible nitric oxide synthase, measured using reverse transcriptase-polymerase chain reaction and western blotting, respectively, were reduced in a concentration-dependent manner. Moreover, the inflammatory cyclooxygenase-2 enzyme expression decreased. Furthermore, the expression of nuclear factor-kappa B ($NF-{\kappa}B$), the key regulator of the transcriptional activation of the inflammatory cytokine genes, was reduced by the RSL chloroform fraction. Therefore, the results of our study suggest that RSL exhibits anti-inflammatory effects in LPS-stimulated macrophages via $NF-{\kappa}B$ inactivation.

• IMMUNE NETWORK
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• v.10 no.4
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• pp.126-134
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• 2010

Background: $CD8^+$ T cells contribute to the clearance of Hepatitis B virus (HBV) infection and an insufficient $CD8^+$ T cell response may be one of the major factors leading to chronic HBV infection. Since the HBx antigen of HBV can up-regulate cellular expression of several immunomodulatory molecules, we hypothesized that HBx expression in hepatocytes might affect $CD8^+$ T cell activity. Methods: We analyzed the activation and apoptosis of $CD8^+$ T cells co-cultured with primary hepatocytes rendered capable of expressing HBx by recombinant baculovirus infection. Results: Expression of HBx in hepatocytes induced low production of $interferon-{\gamma}$ and apoptosis of CD8+ T cells, with no effect on CD8 T cell proliferation. However, transcriptional levels of H-2K, ICAM-1 and PD-1 ligand did not correlate with HBx expression in hepatocytes. Conclusion: Our results suggest that HBx may inhibit $CD8^+$ T cell response by regulation of $interferon-{\gamma}$ production and apoptosis.

• Biomolecules & Therapeutics
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• v.24 no.2
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• pp.140-146
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• 2016

Naringenin (NAR) as one of the flavonoids observed in grapefruit has been reported to exhibit an anti-cancer activity. Activating transcription factor 3 (ATF3) is associated with apoptosis in human colon cancer cells. This study was performed to investigate the molecular mechanism by which NAR stimulates ATF3 expression and apoptosis in human colon cancer cells. NAR reduced the cell viability and induced an apoptosis in human colon cancer cells. ATF3 overexpression increased NAR-mediated cleaved PARP, while ATF3 knockdown attenuated the cleavage of PARP by NAR. NAR increased ATF3 expression in both protein and mRNA level, and increased the luciferase activity of ATF3 promoter in a dose-dependent manner. The responsible region for ATF3 transcriptional activation by NAR is located between -317 and -148 of ATF3 promoter. p38 inhibition blocked NAR-mediated ATF3 expression, its promoter activation and apoptosis. The results suggest that NAR induces apoptosis through p38-dependent ATF3 activation in human colon cancer cells.

• Natural Product Sciences
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• v.20 no.4
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• pp.232-236
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• 2014

Acanthopanax divaricatus var. albeofructus (ADA) is commonly ingested as a traditional medicine or as a component of a health drink in Korea. In this phytochemical study, nine phenolics (1 - 9) and three lignans (10 - 12) were isolated from the MeOH extract of the stems of ADA. Chemical structures were elucidated by comparing spectroscopic data with reported values. Nuclear factor kappa B ($NF-{\kappa}B$) inhibitory activity of the isolated compounds was evaluated using an $NF-{\kappa}B$ luciferase assay in HepG2 cells. Among them, compounds 1, 3 - 8, and 11 showed significant inhibitory effects on $TNF{\alpha}$-induced $NF-{\kappa}B$ transcriptional activity in a dosedependent manner, with $IC_{50}$ values ranging from 13.25 to $37.36{\mu}M$. Further studies on potential anti-inflammatory effects and the benefits of phenolic and lignan components from ADA are warranted.

• Toxicological Research
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• v.22 no.1
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• pp.31-37
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• 2006

It was previously found that melittin inhibited $NF-{\kappa}B$ activity by reacting with signal molecules of $NF-{\kappa}B$ which is critical contributor in cancer cell growth by induction of apoptotic cell death. We here investigated whether melittin inhibits cell growth of human prostate cancer cells through induction of apoptotic cell death, and the possible signal pathways. Melittin ($0{\sim}1\;{\mu}g/ml$) inhibited prostate cancer cell growth in a dose dependent manner. Conversely related to the growth inhibitory effect, melittin increased the induction of apoptotic cell death in a dose dependent manner. Melittin also inhibited DNA binding activity of $NF-{\kappa}B$, an anti-apoptotic transcriptional factor. Consistent with the induction of apoptotic cell death and inhibition of $NF-{\kappa}B$, melittin increased the expression of pro-apoptotic proteins caspase-3, and Bax but down-regulated anti-apoptotic protein Bcl-2. These findings suggest that melittin could inhibit prostate cancer cell growth, and this effect may be related with the induction of apoptotic cell death via inactivation of $NF-{\kappa}B$.

• Proceedings of the Korean Society of Toxicology Conference
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• 2003.05a
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• pp.95.1-95
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• 2003

Ginger (Zingiber officinale Roscoe, Zingiberaceae) has a wide array of pharmacologic effects. Our previous studies have demonstrated that [6]-gingerol, a major pungent ingredient of ginger, inhibits mouse skin tumor promotion and anchorage-independent growth of cultured mouse epidermal cells stimulated with epidermal growth factor. In this study, we have investigated the molecular mechanisms underlying chemopreventive effects of [6]-gingerol on mouse skin carcinogenesis. Cyclooxygenase-2 (COX-2), a key enzyme in the formation of prostaglandins, has been recognized as a molecular target of many chemopreventive as well as anti-inflammatory agents. The murine COX-2 promoter contains several transcriptional elements, particularly those involved in regulating inflammatory processes. One of the essential transcription factors responsible for COX-2 induction is NF-kappa B. Topical application of [6]-gingerol inhibited the COX-2 expression through suppression of NF-kappa B activation in phorbol ester-treated mouse skin. [6]-Gingerol, through down-regulation of p38 MAPK, abrogated the DNA binding activity of NF-kappa B by blocking phosphorylation of p65/RelA at the Ser 536 residue. These findings suggest that [6]-gingerol exerts an anti-tumor promotional activity through inhibition of the p38 MAPK-NF-kappa B siganling cascade in mouse skin.

• Biomedical Science Letters
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• v.20 no.2
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• pp.62-69
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• 2014

Previous our study demonstrated that ailanthoidol (3-deformylated 2-arylbenzo[b]furan), a neolignan from Zanthoxylum ailanthoides or Salvia miltiorrhiza Bunge, is a novel anti-inflammatory agent. In this investigation, we examined the anti-adipogenic effect of ailanthoidol. Our data showed that ailanthoidol suppressed lipid droplet formation and adipocyte differentiation in 3T3-L1 cells. Treatment of the 3T3-L1 adipocytes with ailanthoidol resulted in an attenuation of the releases of leptin and interleukin-6. The expression of peroxisome proliferator-activated receptor $(PPAR){\gamma}$ and CCAAT/enhancer-binding protein $(C/EBP){\alpha}$, the central transcriptional regulators of adipogenesis, was decreased by treatment with ailanthoidol. Additionally, ailanthoidol treatment increased the phosphorylation levels of 5' adenosine monophosphate-activated protein kinase. These results suggest that ailanthoidol effectively suppresses adipogenesis and that it exerts its role mainly through the significant down-regulation of $PPAR{\gamma}$ and $C/EBP{\alpha}$ expression. Our findings provide important insights into the mechanisms underlying the anti-adipogenic activity of ailanthoidol.

• BMB Reports
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• v.46 no.2
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• pp.92-96
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• 2013

The breast cancer susceptibility gene BRCA1 encodes a nuclear protein, which functions as a tumor suppressor and is involved in gene transcription and DNA repair processes. Many families with inherited breast and ovarian cancers have mutations in the BRCA1 gene. However, only a few studies have reported on the mechanism underlying the regulation of BRCA1 expression in humans. In this study, we investigated the transcriptional regulation of BRCA1 in HeLa cells treated with etoposide. We found that three Egr-1-binding sequences (EBSs) were located at -1031, -1005, and -385 within the enhancer region of the BRCA1 gene. Forced expression of Egr-1 stimulated the BRCA1 promoter activity. EMSA data showed that Egr-1 bound directly to the EBS within the BRCA1 gene. Knockdown of Egr-1 through the expression of a small hairpin RNA (shRNA) attenuated etoposide-induced BRCA1 promoter activity. We conclude that Egr-1 targets the BRCA1 gene in HeLa cells exposed to etoposide.