• Korean Journal of Pharmacognosy
• /
• v.38 no.4
• /
• pp.387-393
• /
• 2007

By screening inhibitory activities on the melanin polymer biosynthesis in B-16 mouse melanoma cell lines, MeOH extract of Phellodendri Cortex was found to have inhibitory effect on melanin polymer biosynthesis. Twelve compounds were isolated from the MeOH extract of P. Cortex. They were identified as obacunone (1), limonin (2), ${\beta}-sitosterol$ (3), bis(2-methylheptyl) phthalate (4), cycloeucalenol (5), berberine (6), palmatine (7), jatrorrhizine (8), syringin (9), umbelliferone (10), rutaecarpine (11) and scopoletin (12) by comparison of their physical and spectral data with those of authentic samples. Among the isolated compounds, berberine (6) and palmatine (7) showed potent inhibitory effect on the melanin polymer biosynthesis in cultured B-16 mouse melanoma cell lines, with Inhibition rate of 96% and 90%, respectively. As a positive control, arbutin exhibited an inhibition rate of 56%.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.21 no.1
• /
• pp.181-189
• /
• 2007

To examine the effects of HHCP on atopic dermatitis and its various immunopathologic parameters was induced by DNCB in NC/Nga mice and the animals were orally administrated with HHCP. We summarized the results obtained from serum levels of IgE and the numbers of various immune cells as follow. HHCP has no cytotoxic effects at the range of concentration (1-400 ${\mu}g$/ml) on fibroblast isolated from lung of BALB/c mice. HHCP significantly lowered the serum levels of IgE compared with control at 16 and 20 week. HHCP significantly reduced the number of CD19$^+$ cell in spleen and DLN, as well as the number of B220$^+$ /IgE$^+$ cell in DLN compared with control. HHCP significantly reduced the number of ${\alpha}$${\beta}$ TCR$^+$ in spleen and DLN, the number of CD8$^+$ in spleen compared with control, and also significantly reduced the number of CD3$^+$, CCR3, CD3$^+$/CD69$^+$, CD3/ CCR3, CD4$^+$, CD3$^+$/ CD4$^+$/CD45$^+$ cell in DLN. HHCP increased the number of NK$^+$ cells in spleen compared with control, in contrast significantly decreased the number of CD11c$^+$/ Classll$^+$ cell and CD11b$^+$/Gr-1$^+$ cell in DLN. Taken together, these results suggested that HHCP has suppressive effects on atopic dermatitis through the inhibition of IgE production and modulation of immune cell population in NC/Nga mice.

• Journal of Industrial Technology
• /
• v.25 no.B
• /
• pp.241-251
• /
• 2005

Exopolysaccharide (CBP) from submerged culture broth of Ganoderma lucidum mycelium and the water soluble (BWS) and water insoluble (BWI) fractions of CBP were prepared by gel filtration. Antitumor activity and effects on proliferation and differenciation of human cancer cells and mouse NIH 3T3 cells were studied. Cytotoxicity test of CBP, BWS and BWI fractions on human cancer cell lines was performed by using sulforhodamine B (SRB) assay. A549 (lung carcinoma), Colo320 DM and HSR (colon carcinoma), and NIH 3T3 cells were used. BWI fraction showed the strongest cytotoxicity (maximum 20% survival) to all human cells tested. However it did not induced apoptosis. Interestingly BWI fraction did not exert cytotoxic effect on NIH 3T3 cells at low concentration of cells ($5{\times}10^4$) but strong toxic effect at high concentration of cells($5{\times}10^5$) which showed transformed morphology. These results suggest that BWI may have cancer cell specific anticancer activity. However, BWI fraction did not effect the amount of pRb and c-myc protein, which implied that BWI fraction did not act at the early stage of signal transduction pathway. CBP fraction induced differenciation of human leukemic cell line, HL-60 cells suggesting the carcinogenesis prevention of normal cell and possible induction of normalization for cancer cell.

• International Journal of Oral Biology
• /
• v.38 no.1
• /
• pp.37-42
• /
• 2013

Receptor activator of NF-${\kappa}B$ ligand (RANKL) is an essential cytokine for osteoclast differentiation, activation and survival. T lymphocytes such as $T_{17}$ cells, a subset of T helper cells that produce IL-17, play an important role in rheumatoid arthritic bone resorption by producing inflammatory cytokines and RANKL. It has not yet been clearly elucidated how T cell activation induces RANKL expression. T cell receptor activation induces the activation of nuclear factor of activated T cell (NFAT) and expression of its target genes. In this study, we examined the role of NFAT in T cell activation-induced RANKL expression. EL-4, a murine T lymphocytic cell line, was used. When T cell activation was induced by phorbol 12-myristate 13-acetate (PMA) and ionomycin, RANKL expression increased in a time-dependent manner. In the presence of cyclosporin, an inhibitor of NFAT activation, this PMA/ionomycin-induced RANKL expression was blocked. Overexpression of either NFATc1 or NFATc3 induced RANKL expression. Chromatin immunoprecipitation results demonstrated that PMA/ionomycin treatment induced the binding of NFATc1 and NFATc3 to the mouse RANKL gene promoter. These results suggest that NFATc1 and NFATc3 mediates T cell receptor activation-induced RANKL expression in T lymphocytes.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.33 no.9
• /
• pp.1439-1444
• /
• 2004

Antitumor activities of onion methanol extract (OME) and onion Kimchi methanol extract (OKME) were investigated by using aflatoxin $B_1$-mediated Salmonella typhimurium mutagenicity and the model of cytotoxicity on the cancer cell lines. Their immune activities were also investigated by using mouse spleen cells and macrophage cell lines, respectively. OME and OKME showed the enhanced antimutagenicity in a dose-dependent manner in particular, the activity of OKME was higher than that of OME. OME and OKME decreased over 20% of the proliferation of the A549 (lung cancer cell) and MCF-7 (breast cancer cell) cell lines when compared with the control at 1,000 ${\mu}$g/mL. The proliferation of mouse spleen cells and the NO production in marcrophage cell lines treated OME and OKME were increased in a dose-dependent manner compared with untreated control cells, and their activities of OKME were higher than those of OME.

• Food Science and Preservation
• /
• v.12 no.2
• /
• pp.173-178
• /
• 2005

Antitumor activities of methanol extract from onion Kochujang (MEOK) were investigated by using aflatoxin $B_{1}-mediated$ Salmonella typhimurium mutagenicity and the model of cytotoxicity on the cancer cell lines. Their immune activities were also investigated using mouse spleen cells and macrophage cell lines, respectively. MEOK showed the enhanced antimutagenicity in a dose-dependent manner. relative to the control group. MEOK decreased over $20\%$ of the proliferation of the A549(lung cancer cell) and MCF(breast cancer cell) cell lines at $1,000\;{\mu}g/mL$ concentration compared with the control cells. The proliferation of mouse spleen cells and the NO production in marcrophage cell lines treated MEOK were increased in a dose-dependent manner, respectively. The activities were higher than that of the control(no added onion) Kochujang.

• Development and Reproduction
• /
• v.25 no.1
• /
• pp.15-24
• /
• 2021

Benzo[a]pyrene (B[a]P) is a potent carcinogen and is classified as an endocrine-disrupting chemical. In mammalian testes, Sertoli cells support spermatogenesis. Therefore, if these cells are negatively affected by exposure to xenotoxic chemicals, spermatogenesis can be seriously disrupted. In this context, we evaluated whether mouse testicular TM4 Sertoli cells are susceptible to the induction of cytotoxicity-mediated cell death after exposure to B[a] P in vitro. In the present study, while B[a]P and B[a]P-7,8-diol were not able to induce cell death, exposure to BPDE resulted in cell death. BPDE-induced cell death is accompanied by the activation of caspase-3 and caspase-7. Depolarization of the mitochondrial membrane and cytochrome c release from mitochondria were observed in benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE)-treated cells. These results indicate that TM4 cells are susceptible to apoptosis in a caspase-dependent manner. Western blot and reverse transcription-polymerase chain reaction (RT-PCR) analyses showed that aryl hydrocarbon receptor (AhR) expression was almost undetectable in TM4 cells and that its expression was not altered after B[a]P treatment. This indicates that TM4 cells are nearly AhR-deficient. In TM4 cells, the CYP1A1 protein and its activity were not present. From these results, it is clear that AhR may be a prerequisite for CYP1A1 expression in TM4 cells. Therefore, TM4 cells can be referred to as CYP1A1-deficient cells. Thus, TM4 Sertoli cells are believed to have a rigid and protective cellular machinery against genotoxic agents. In conclusion, it is suggested that tolerance to B[a]P cytotoxicity is associated with insufficient AhR and CYP1A1 expression in testicular Sertoli cells.

• Biomolecules & Therapeutics
• /
• v.32 no.1
• /
• pp.84-93
• /
• 2024

Rosmarinic acid (RA) is a phenolic ester that protects human keratinocytes against oxidative damage induced by ultraviolet B (UVB) exposure, however, the mechanisms underlying its effects remain unclear. This study aimed to elucidate the cell signaling mechanisms that regulate the antioxidant activity of RA and confirm its cyto-protective role. To explore the signaling mechanisms, we used the human keratinocyte cell line HaCaT and SKH1 hairless mouse skin. RA enhanced glutamate-cysteine ligase catalytic subunit (GCLC) and glutathione synthetase (GSS) expression in HaCaT cells in a dose- and time-dependent manner. Moreover, RA induced nuclear factor erythroid-2-related factor 2 (NRF2) nuclear translocation and activated the signaling kinases protein kinase B (AKT) and extracellular signal-regulated kinase (ERK). Treatment with the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, the ERK inhibitor U0126, and small interfering RNA (siRNA) gene silencing suppressed RA-enhanced GCLC, GSS, and NRF2 expression, respectively. Cell viability tests showed that RA significantly prevented UVB-induced cell viability decrease, whereas the glutathione (GSH) inhibitors buthionine sulfoximine, LY294002, and U0126 significantly reduced this effect. Moreover, RA protected against DNA damage and protein carbonylation, lipid peroxidation, and apoptosis caused by UVB-induced oxidative stress in a concentration-dependent manner in SKH1 hairless mouse skin tissues. These results suggest that RA protects against UVB-induced oxidative damage by activating AKT and ERK signaling to regulate NRF2 signaling and enhance GSH biosynthesis. Thus, RA treatment may be a promising approach to protect the skin from UVB-induced oxidative damage.

• Journal of Life Science
• /
• v.21 no.6
• /
• pp.767-774
• /
• 2011

Cell migration plays a fundamental role in cancer cell invasion and metastasis as well as in many physiological responses. Here, we screened four different sources of garlic - water extract of normal and black garlic, as well as dried normal and black garlic - for the identification of anti-invasive and anti-metastatic activity on cancer cells. Inhibition of cancer cell migration was observed in the hexane extract of dried-garlic. Inhibitory activity was further purified to near homogeneity by thin layer chromatography and named $\b{i}$nhibitor of $\b{c}$ancer $\b{m}$etastasis from garlic #27 (ICMG-27). ICMG-27 completely blocked insulin-like growth factor-1 (IGF-1)-induced OVCAR-3 cell migration at 6 ${\mu}g/ml$. ICMG-27 completely blocked IGF-1-induced OVCAR-3 and NIH-3T3 cell migration whereas IGF-1-induced mouse embryonic fibroblast (MEF) cell migration was not affected byICMG-27. ICMG-27 inhibited all the tested IGF-1-induced cancer cell migration such as OVCAR-3, SKOV-3, and MDA-MB-231 cells. Finally, ICMG-27 could inhibit IGF-1-, lysophosphatidic acid (LPA)-, sphingosine-1-phosphate (S1P)-, leukotriene B4 (LTB4)-, and angiotensin II (AngII)-induced OVCAR-3 cell migration. These results indicate that ICMG-27 inhibits cancer cell migration by blocking essential steps in many agonists-induced cancer cell migrations. Unveiling an anti-invasive mechanism of ICMG-27 on cancer cells will provide a basis for cancer therapy.

• Journal of Life Science
• /
• v.23 no.10
• /
• pp.1199-1208
• /
• 2013

Fibroblastic reticular cells (FRCs) form the structural backbone of the T zone provide a guidance path for immigrating T cells in the lymph node (LN). FRCs may contribute directly to developing T-cell biology in the LN and allow analyses of fundamental aspects of FRC biology related to T cells. FRCs inhibited T-cell apoptosis, and FRC culture supernatants strongly induced the expression of Bcl-xL in T cells against doxorubicin. Coculture of FRC and T cells resulted in rearrangements of the actin cytoskeleton, as well as global changes in the morphology of the FRCs. In addition, when cocultured, the T cells adhered to the FRC monolayer, and the membrane intercellular adhesion molecule (ICAM)-1 was slightly increased by day-dependent manner. In contrast, the expression of soluble ICAM-1 was dramatically increased in a day-dependent manner. Several chemokines, such as CCL5, CXCL1, CXCL5, CXCL16, CCL8, CXCL13, and ICAM-1, and MMPs were expressed in FRCs sensed by tumor necrosis factor (TNF) families. Nuclear factor kappa B ($NF{\kappa}B$)-RelA of the $NF{\kappa}B$ canonical pathway was translocated into FRC nuclear by $TNF{\alpha}$. In contrast, p52 proteolyzed from p100, a counterpart of RelB of the noncanonical $NF{\kappa}B$ pathway, accumulated in the peripheral FRC nucleus by agonistic anti-$LT{\beta}R$ antibody. In summary, we propose a model in which FRCs engage in bidirectional crosstalk to increase the efficiency of T-cell biology. This cooperative feedback loop may help to maintain tissue integrity and function during immune responses.