Jung Ok Ban

Chungbuk National University, Chinsen, Chungcheongbuk-do, South Korea

Are you Jung Ok Ban?

Claim your profile

Publications (30)119.47 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Interleukin (IL)-32, mainly produced by T-lymphocytes, natural killer cells, epithelial cells, and blood monocytes, is dominantly known as a pro-inflammatory cytokine. However, the role of IL-32 on inflammatory disease has been doubtful according to diverse conflicting results. This study was designed to examine the role of IL-32β on the development of collagen antibody (CAIA) and lipopolysaccharide (LPS)-induced inflammatory arthritis. Our data showed that the paw swelling volume and clinical score were significantly reduced in the CAIA and LPS-treated IL-32β transgenic mice compared with non-transgenic mice. The populations of cytotoxic T, NK and dendritic cells was inhibited and NF-κB and STAT3 activities were significantly lowered in the CAIA and LPS-treated IL-32β transgenic mice. The expression of pro-inflammatory proteins was prevented in the paw tissues of CAIA and LPS-treated IL-32β transgenic mice. In addition, IL-32β altered several cytokine levels in the blood, spleen and paw joint. Our data indicates that IL-32β comprehensively inhibits the inflammation responses in the CAIA and LPS-induced inflammatory arthritis model.
    Oncotarget 10/2015; DOI:10.18632/oncotarget.6160 · 6.36 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Activation of nuclear factor kappa-B (NF-κB) is implicated in drug resistant of lung cancer cells. Our previous data showed that thiacremonone inhibited activation of NF-κB. In the present study, we investigated whether thiacremonone enhanced susceptibility of lung cancer cells to a common anti-cancer drug paclitaxel by further inhibition of NF-κB. Thus, we used the threefold lower doses of IC50 values (50 μg/ml thiacremonone and 2.5 nM paclitaxel). We found that combination treatment with thiacremonone and paclitaxel was more susceptible (combination index; 0.40 in NCI-H460 cells and 0.46 in A549 cells) in cell growth inhibition of two types of lung cancer cell lines compared to a single agent treatment. Consistent with the combination effect on cancer cell growth inhibition, the combination treatment further induced apoptotic cell death and arrested the cancer cells in G2/M phase accompanied with a much lower expression of cdc2 and cyclin B1, and inhibited colony formation. Much more inactivation of NF-κB and greater expression of NF-κB target apoptosis regulated genes such as caspase-8 and PARPs were found by the combination treatment. Molecular model and pull down assay as well as MALDI-TOF analysis demonstrated that thiacremonone directly binds to p50. These data indicated that thiacremonone leads to increased apoptotic cell death in lung cancer cell lines through greater inhibition of NF-κB by the combination treatment with paclitaxel.
    Archives of Pharmacal Research 03/2015; 38(7). DOI:10.1007/s12272-015-0589-4 · 2.05 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The purpose of this study was to evaluate the anticancer efficacy of cetuximab combined with cisplatin (combination treatment) on colon cancer growth, as well as its underlying action mechanism. Combination treatment synergistically potentiated the effect of cetuximab on cell growth inhibition and apoptosis induction in HCT116 and SW480 cells. Combination treatment further suppressed the expression of the activated form of epidermal growth factor receptor (EGFR) and MAP kinase (p-ERK and p-p38) and also significantly inhibited the activity of activator protein-1 (AP-1) and nuclear factor kappa B (NF- κ B). Additionally, the expression of cyclooxygenase-2 (COX-2) and interleukin-8 (IL-8) mRNA was significantly reduced by the combination treatment as compared to the expression seen for treatment with cetuximab or cisplatin alone. We found that the synergistic inhibitory effects of cetuximab and cisplatin on AP-1 and NF- κ B activation, as well as on cell viability, were reversed by pretreatment with an ERK inhibitor. Results demonstrate that combined treatment with cetuximab and cisplatin exerts synergistic anticancer effects on colon cancer cells and also suggest that the ERK pathway plays a critical role in these effects via the suppression of the EGFR signaling pathway, along with the inhibition of COX-2, IL-8, and AP-1 and NF- κ B.
    01/2015; 2015(18):1-13. DOI:10.1155/2015/397563
  • [Show abstract] [Hide abstract]
    ABSTRACT: Maillard reaction products are known to have anti inflammatory property. Objective of this study was to assess anti-arthritis effects of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal and its action mechanisms. Lipopolysaccharide (LPS)-activated macrophage (RAW264.7) and synoviocytes were treated with (E)-2,4-bis(p-hydroxyphenyl)-2-butenal for in vitro assay. (E)-2,4-bis(p-hydroxyphenyl)-2-butenal (5 mg/kg) was also periorally administered for 30 days to collagen (50 μg/g) induced arthritic mice. Clinical score, histopathological exam, NO generation, iNOS and COX2 expression, and NF-κB/IKK and STAT3 activities were determined in cultured cell and joint tissues of mice. Binding of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal to STAT3 was evaluated by a Pull-down assay and its binding site was predicted using molecular docking study with Autodock VINA. (E)-2,4-bis(p-hydroxyphenyl)-2-butenal (2.5-10 μg/ml) inhibited LPS (1 μg/ml)-induced NO generation, iNOS and COX2 expression, and NF-κB/IKK and STAT3 activities in macrophage and synoviocytes. (E)-2,4-bis(p-hydroxyphenyl)-2-butenal suppressed the collagen induced arthritic responses through inhibition of the expression of iNOS and COX2, and NF-κB/IKK and STAT3 activities, and also reduced the extent of bone destruction and fibrosis in joint tissues. A Pull-down assay proved that (E)-2,4-bis(p-hydroxyphenyl)-2-butenal interfere with the binding of ATP to STAT3. Subsequent docking study proposes that (E)-2,4-bis(p-hydroxyphenyl)-2-butenal binds to the the DNA binding interface of STAT3 possibly causing ATP binding to STAT3 in an allosteric manner. (E)-2,4-bis(p-hydroxyphenyl)-2-butenal exerted its anti-inflammatory and anti-arthritic effects through inhibition of NF-κB/STAT3 pathway via direct binding to STAT3, and that it could be a useful agent for the treatment of arthritic disease.
    British Journal of Pharmacology 02/2014; 171(11). DOI:10.1111/bph.12619 · 4.84 Impact Factor
  • J.- H. Shim · S.- S. Nah · J. O. Ban · J. T. Hong · S. J. Lee · H.- J. Kim ·
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Maillard reaction products (MRPs) are known to have antioxidant, antimutagenic and anticardiogenic activities. The antioxidant capacity of MRPs is comparable to those of commonly used food antioxidants; butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) and a-tocopherol. Maillard reaction (MR) could produce non-enzymatically colored or colorless products such as glucose-tyrosine, glucose-lysine, fructose-lysine, ribose-lysine, xylose-arginine, xylose-glycine and xylose-tryptophanRecently, we synthesized (E)-2,4-bis(p-hydroxyphenyl)-2-butenal using tyrosine and fructose under a typical MR condition of high temperature and pressure. Objectives Objective of this study was to assess anti-arthritis effects of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal and its action mechanisms.In the present study, we investigated whether (E)-2,4-bis(p-hydroxyphenyl)-2-butenal can have anti-inflammatory activity and anti-arthritic activities through inhibition of NF-kB/IKK and STAT3 pathways in cultured macrophage and synoviocytes, and collagen-induced arthritis (CIA) animal model. Methods Nitric oxide (NO) and prostaglandin E2 assay, electrophoretic mobility shift assay, luciferase assay, Western blot, real-time PCR and pull-down assay were used for mechanism studies. Anti-inflammatory effect was done in cultured RAW 264.7 cells and synoviocytes, and collagen-induced arthritis model was used for evaluation of anti-inflammation and anti-arthritis effects in vivo. Binding target of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal was identified using pull-down assay and sol-gel biochip assay, and its binding site was proposed through a docking experiment. Results (E)-2,4-bis(p-hydroxyphenyl)-2-butenal (2.5-10 mg/ml) inhibited lipopolysaccharides (1 mg/ml)-induced pro-inflammatory responses through downregulating IkB kinase b (IKKb)/nuclear factor-kapaB (NF-kB) and signal transducer and activator of transcription 3 (STAT3) pathways in RAW 264.7 cells and synoviocytes. (E)-2,4-bis(p-hydroxyphenyl)-2-butenal not only suppressed the collagen (100 mg/0.1ml)-induced arthritic responses through inhibition of IKKb/NF-kB and STAT3 activities but also reduced the extent of bone destruction and fibrosis in joint tissue. The population of white blood cells in blood and NO generation in murine splenic T cells of collagen-induced arthritic mice were significantly reduced by (E)-2,4-bis(p-hydroxyphenyl)-2-butenal. Sol-gel biochip analysis proved that (E)-2,4-bis(p-hydroxyphenyl)-2-butenal directly binds to IKKb, and thus inhibit its activity. A docking experiment and pull-down assay indicate that IKKb might be a potential target of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal. Conclusions These findings indicated that (E)-2,4-bis(p-hydroxyphenyl)-2-butenal exerted its anti-inflammatory and anti-arthritic effects through inhibition of IKKb/NF-kB activity via direct binding to IKKb, and that it could be a useful agent for the treatment of arthritic diseases. Disclosure of Interest None Declared
    Annals of the Rheumatic Diseases 01/2014; 71(Suppl 3):673-673. DOI:10.1136/annrheumdis-2012-eular.601 · 10.38 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The medicinal properties of functionally active organosulfur compounds such as allin, diallyl disulfide, S-allylmercaptocysteine, and S-trityl-L-cysteine isolated from garlic have received great attention by the large number of investigators who have studied their pharmacological effects for the treatment of various diseases. These organosulfur compounds are able to prevent for development of cancer, cardiovascular, neurological, and liver disease as well as allergy and arthritis. There have been also many reports on toxicities and pharmacokinetics of these compounds. The aim of this study is to review a variety of experimental and clinical reports, and describe the effectiveness, toxicities and pharmacokinetics, and possible mechanisms of pharmaceutical actions of functionally active compounds isolated from garlic.
    Pharmacology [?] Therapeutics 12/2013; 142(2). DOI:10.1016/j.pharmthera.2013.12.005 · 9.72 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The Maillard reaction products are known to be effective in chemoprevention. Here, we focused on the anti-cancer effects of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal on in vitro and in vivo colon cancer. We analysed the anti-cancer activity of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal on colon cancer cells by using cell cycle and apoptosis analysis. To elucidate it's mechanism, NF-κB DNA binding activity, docking model as well as pull-down assay. Further, a xenograft model of colon cancer was studied to test the in vivo effects of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal. (E)-2,4-Bis(p-hydroxyphenyl)-2-butenal inhibited colon cancer cells (SW620 and HCT116) growth followed by induction of apoptosis in a concentration-dependent manner via down-regulation of NF-κB activity. In docking model as well as pull-down assay, (E)-2,4-bis(p-hydroxyphenyl)-2-butenal directly binds to three amino acid residues of IKKβ, thereby inhibited IKKβ activity in addition to induction of death receptor 6 (DR6) as well as their target apoptotic genes. Finally, (E)-2,4-bis(p-hydroxyphenyl)-2-butenal suppressed anchorage-independent cancer cell growth, and tumor growth in xenograft model accompanied with apoptosis through inhibition of IKKβ/NF-κB activity, and overexpression of DR6. These results suggest that (E)-2,4-bis(p-hydroxyphenyl)-2-butenal inhibits colon cancer cell growth through inhibition of IKKβ/NF-κB activity and induction of DR6 expression.
    Apoptosis 09/2013; 19(1). DOI:10.1007/s10495-013-0903-x · 3.69 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: High doses of acetaminophen (APAP; N-acetyl-p-aminophenol) cause severe hepatotoxicity after metabolic activation by cytochrome P450 2E1. This study was undertaken to examine the preventive effects of thiacremonone, a compound extracted from garlic, on APAP-induced acute hepatic failure in male C57BL/6J. Mice received with 500 mg/kg APAP after a 7-day pretreatment with thiacremonone (10-50 mg/kg). Thiacremonone inhibited the APAP-induced serum ALT and AST levels in a dose-dependent manner, and markedly reduced the restricted area of necrosis and inflammation by administration of APAP. Thiacremonone also inhibited the APAP-induced depletion of intracellular GSH, induction of nitric oxide, and lipid peroxidation as well as expression of P450 2E1. After APAP injection, the numbers of Kupffer cells, natural killer cells, and cytotoxic T cells were elevated, but the elevated cell numbers in the liver were reduced in thiacremonone pretreated mice. The expression levels of I-309, M-CSF, MIG, MIP-1 α , MIP-1 β , IL-7, and IL-17 were increased by APAP treatment, which were inhibited in thiacremonone pretreated mice. These data indicate that thiacremonone could be a useful agent for the treatment of drug-induced hepatic failure and that the reduction of cytotoxic immune cells as well as proinflammatory cytokine production may be critical for the prevention of APAP-induced acute liver toxicity.
    Evidence-based Complementary and Alternative Medicine 07/2013; 2013:974794. DOI:10.1155/2013/974794 · 1.88 Impact Factor
  • Source
    H-M Yun · J H Oh · J-H Shim · J O Ban · K-R Park · J-H Kim · D H Lee · J-W Kang · Y H Park · D Yu · Y Kim · S B Han · D-Y Yoon · J T Hong ·
    [Show abstract] [Hide abstract]
    ABSTRACT: Cytokine and activation of lymphocytes are critical for tumor growth. We investigated whether interleukin (IL)-32β overexpression changes other cytokine levels and activates cytotoxic lymphocyte, and thus modify tumor growth. Herein, IL-32β inhibited B16 melanoma growth in IL-32β-overexpressing transgenic mice (IL-32β mice), and downregulated the expressions of anti-apoptotic proteins (bcl-2, IAP, and XIAP) and cell growth regulatory proteins (Ki-67 antigen (Ki-67) and proliferating cell nuclear antigen (PCNA)), but upregulated the expressions of pro-apoptotic proteins (bax, cleaved caspase-3, and cleaved caspase-9). IL-32β also inhibited colon and prostate tumor growth in athymic nude mice inoculated with IL-32β-transfected SW620 colon or PC3 prostate cancer cells. The forced expression of IL-32β also inhibited cell growth in cultured colon and prostate cancer cells, and these inhibitory effects were abolished by IL-32 small interfering RNA (siRNA). IL-10 levels were elevated, but IL-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) levels were reduced in the tumor tissues and spleens of IL-32β mice, and athymic nude mice. The number of cytotoxic T (CD8(+)) and natural killer (NK) cells in tumor tissues, spleen, and blood was significantly elevated in IL-32β mice and athymic nude mice inoculated with IL-32β-transfected cancer cells. Constituted activated NF-κB and STAT3 levels were reduced in the tumor tissues of IL-32β mice and athymic nude mice, as well as in IL-32β-transfected cultured cancer cells. These findings suggest that IL-32β inhibits tumor growth by increasing cytotoxic lymphocyte numbers, and by inactivating the NF-κB and STAT3 pathways through changing of cytokine levels in tumor tissues.
    Cell Death & Disease 05/2013; 4(5):e640. DOI:10.1038/cddis.2013.166 · 5.01 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The Maillard Reaction Products (MRPs) are chemical compounds which have been known to be effective in chemoprevention. Death receptors (DR) play a central role in directing apoptosis in several cancer cells. In our previous study, we demonstrated that (E)-2,4-bis(p-hydroxyphenyl)-2-butenal, a MRP product, inhibited human colon cancer cell growth by inducing apoptosis via nuclear factor-κB (NF-κB) inactivation and G2/M phase cell cycle arrest. In this study, (E)-2,4-bis(p-hydroxyphenyl)-2-butenal diacetate, a new (E)-2,4-bis(p-hydroxyphenyl)-2-butenal derivative, was synthesized to improve their solubility and stability in water and then evaluated against NCI-H460 and A549 human lung cancer cells. (E)-2,4-bis(p-hydroxyphenyl)-2-butenal diacetate reduced the viability in both cell lines in a time and dose-dependent manner. We also found that (E)-2,4-bis(p-hydroxyphenyl)-2-butenal diacetate increased apoptotic cell death through the upregulation of the expression of death receptor (DR)-3 and DR6 in both lung cancer cell lines. In addition to this, the transfection of DR3 siRNA diminished the growth inhibitory and apoptosis inducing effect of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal diacetate on lung cancer cells, however these effects of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal diacetate was not changed by DR6 siRNA. These results indicated that (E)-2,4-bis(p-hydroxyphenyl)-2-butenal diacetate inhibits human lung cancer cell growth via increasing apoptotic cell death by upregulation of the expression of DR3.
    Biomolecules and Therapeutics 11/2012; 20(6):538-43. DOI:10.4062/biomolther.2012.20.6.538 · 1.73 Impact Factor
  • N J Lee · J H Oh · J O Ban · J H Shim · H P Lee · J K Jung · B W Ahn · DY Yoon · S B Han · YW Ham · J T Hong ·
    [Show abstract] [Hide abstract]
    ABSTRACT: Background and purpose: The effects of 4-O-methylhonokiol (MH), a constituent of Magnolia officinalis, were investigated on human prostate cancer cells and its mechanism of action elucidated. Experimental approach: The anti-cancer effects of MH were examined in prostate cancer and normal cells. The effects were validated in vivo using a mouse xenograft model. Key results: MH increased the expression of PPARγ in prostate PC-3 and LNCap cells. The pull-down assay and molecular docking study indicated that MH directly binds to PPARγ. MH also increased transcriptional activity of PPARγ but decreased NF-κB activity. MH inhibited the growth of human prostate cancer cells, an effect attenuated by the PPARγ antagonist GW9662. MH induced apoptotic cell death and this was related to G(0) -G(1) phase cell cycle arrest. MH increased the expression of the cell cycle regulator p21, and apoptotic proteins, whereas it decreased phosphorylation of Rb and anti-apoptotic proteins. Transfection of PC3 cells with p21 siRNA or a p21 mutant plasmid on the cyclin D1/ cycline-dependent kinase 4 binding site abolished the effects of MH on cell growth, cell viability and related protein expression. In the animal studies, MH inhibited tumour growth, NF-κB activity and expression of anti-apoptotic proteins, whereas it increased the transcriptional activity and expression of PPARγ, and the expression of apoptotic proteins and p21 in tumour tissues. Conclusions and implication: MH inhibits growth of human prostate cancer cells through activation of PPARγ, suppression of NF-κB and arrest of the cell cycle. Thus, MH might be a useful tool for treatment of prostate cancer.
    British Journal of Pharmacology 10/2012; 168(5). DOI:10.1111/j.1476-5381.2012.02235.x · 4.84 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Garlic is widely used as a spice. Garlic extracts exert anticancer and antiinflammatory effects, but its antiobesity efficacy studies have produced conflicting results. The antiobesity effects of thiacremonone, a sulfur compound isolated from garlic, was evaluated in obese db/db mice. Thiacremonone was orally administrated to mice for 3 weeks. The thiacremonone-treated db/db mice showed a loss of body weight and decrease in blood triglyceride and glucose levels compared with the control mice. Histological analysis further revealed that thiacremonone significantly decreased lipid accumulation in the fatty livers of treated db/db mice. It was observed that GLUT-4 expression and glucose uptake were up-regulated by thiacremonone in 3T3-L1 adipocytes. Thiacremonone treatment also suppressed expression levels of acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), which are involved in lipid metabolism, in the liver of db/db mice. In addition, thiacremonone enhanced peroxisome proliferator-activated receptor γ (PPARγ) expression in the fatty liver. Taken together, these results suggest that thiacremonone may play a vital role in improving the management of obesity and related metabolic syndromes via inhibition of lipid accumulation. Copyright © 2012 John Wiley & Sons, Ltd.
    Phytotherapy Research 09/2012; 26(9):1265-71. DOI:10.1002/ptr.3729 · 2.66 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Resveratrol (Res), from the skin of red grapes, induces apoptosis in some malignant cells, but there are no reports on the apoptotic effect of Res on human malignant pleural mesothelioma. We found that Res interacts with specificity protein 1 (Sp1). The IC50 for Res was 17 µM in MSTO-211H cells. Cell viability was decreased and apoptotic cell death was increased by Res (0-60 µM). Res increased the Sub-G1 population in MSTO-211H cells and significantly suppressed Sp1 protein levels, but not Sp1 mRNA levels. Res modulated the expression of Sp1 regulatory proteins including p21, p27, cyclin D1, Mcl-1 and survivin in mesothelioma cells. After treatment with Res, apoptosis signaling cascades were activated by the activation of Bid, Bim, caspase-3 and PARP, upregulation of Bax and downregulation of Bcl-xL. Res (20 mg/kg daily for 4 weeks) effectively suppressed tumor growth in vivo in BALB/c athymic (nu+/nu+) mice injected with MSTO-211H cells, an effect that was mediated by inhibition of Sp1 expression and induction of apoptotic cell death. Our results strongly suggest that Sp1 is a novel molecular target of Res in human malignant pleural mesothelioma.
    International Journal of Molecular Medicine 04/2012; 30(1):21-7. DOI:10.3892/ijmm.2012.978 · 2.09 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Garlic extracts exert anti-cancer and anti-inflammatory effects. However, the anti-adipogenic effect of garlic-derived compounds remains unclear. In this study, we examined the effect of thiacremonone, a sulfur compound isolated from garlic, on adipocyte differentiation using 3T3-L1 cells. We found that thiacremonone significantly inhibited 3T3-L1 differentiation via down-regulation of adipogenesis-related transcription factors and adipogenic markers. The inhibitory effect mainly occurred at the early phase of differentiation in 3T3-L1 cells. There was no cytotoxic effect of thiacremonone in 3T3-L1 cells and treatment of differentiating 3T3-L1 cells with thiacremonone resulted in AMPK activation, which led to an attenuated expression of acetyl CoA carboxylase-1 (ACC-1), an essential enzyme for the synthesis and usage of fatty acids. Moreover, thiacremonone enhanced the mRNA level of carnitine palmitoyltransferase (CPT-1). The modulating effect of thiacremonone on expressions of genes involved in lipolysis was partially abrogated by treatment with compound C, an AMPK inhibitor. Taken together, these results indicated that thiacremonone-induced AMPK activation, inhibition of ACC-1 expression and concomitant recovery of CPT-1 expression resulted in the suppression of intracellular lipid droplet levels, suggesting that thiacremonone may induce reduction of lipid synthesis and increases in fatty acid oxidation partially mediated via AMPK activation. Thiacremonone may be a promising compound for the treatment of obesity.
    The Journal of nutritional biochemistry 03/2012; 23(12). DOI:10.1016/j.jnutbio.2011.10.008 · 3.79 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We isolated a substance from fructose–tyrosine Maillard reaction products (MRPs) and investigated its antiproliferative effect on six human cancer cell lines. The ethyl acetate fraction of fructose–tyrosine MRPs showed a strong antiproliferative effect; this fraction was isolated and purified using silica gel column chromatography, semipreparative RP-HPLC, and recycling HPLC. The structure of the purified compound was determined using spectroscopic methods. The isolated compound was identified as 2,4-bis(p-hydroxyphenyl)-2-butenal (C16H14O3, HPB242). HPB242 inhibited cell growth in a dose-dependent manner (10–80 μg/ml) on the six human cancer cell lines. The IC50 values of HPB242 on the six human cancer cell lines were 17.34 μg/ml (MCF-7), 29.21 μg/ml (HCT-116), 34.57 μg/ml (H-460), 34.87 μg/ml (HepG2), 48.77 μg/ml (PC-3), and 55.83 μg/ml (MKN-45).
    Food Chemistry 02/2012; 130(3):547–551. DOI:10.1016/j.foodchem.2011.07.068 · 3.39 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: PPARγ ligands have been reported to reduce proliferation of human prostate cancer cells. However, the molecular mechanism of PPARγ agonist-induced cell growth inhibition of prostate cancer cells is not clear. GSK-3β expression and NFκB activity have important roles in prostate cancer development. To investigate the mechanisms of the PPARγ agonist-induced prostate cancer cell growth inhibition, we examined the effect of troglitazone on the expression of PPARγ, GSK-3β and activity of NFκB as well as on the prostate cancer cell growth. Troglitazone induced the expression of PPARγ in the nuclear of PC-3 cells, but not in LNCaP cells. Troglitazone (0-16 uM) inhibited cancer cell growth in a similar extend between both cells accompanied by the induction of cell cycle arrest in G(0)/G(1) phase and an increased in the similar extent of apoptotic cell death in concentration dependent manner. Troglitazone inhibited the constitutive expression of GSK-3β and activation of NFκB. Co-treatment of troglitazone with a GSK-3β inhibitor (AR-a014418) or GSK-3β siRNA significantly augmented the inhibitory effect of troglitazone on the NFκB activity and on prostate cancer cell growth inhibition and apoptotic cell death. However, overexpression of GSK-3β hindered troglitazone-induced cell growth inhibition and NFκB inactivation. These results suggest that PPARγ agonist, troglitazone, inhibits prostate cancer cell growth through inactivation of NFκB via suppression of GSK-3β expression.
    Cancer biology & therapy 08/2011; 12(4):288-96. DOI:10.4161/cbt.12.4.15961 · 3.07 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Biphenolic components in the Magnolia family have shown several pharmacological activities such as antitumor effects. This study investigated the effects of 4-O-methylhonokiol (MH), a constituent of Magnolia officinalis, on human colon cancer cell growth and its action mechanism. 4-O-methylhonokiol (0-30 μM) decreased constitutive activated nuclear factor (NF)-κB DNA binding activity and inhibited growth of human colon (SW620 and HCT116) cancer cells. It also caused G₀-G₁ phase cell cycle arrest followed by an induction of apoptotic cell death. However, knockdown with small interfering RNA (siRNA) of p21 or transfection with cyclin D1/Cdk4 binding site-mutated p21 abrogated MH-induced cell growth inhibition, inhibition of NF-κB activity as well as expression of cyclin D1 and Cdk4. Conversely, inhibition of NF-κB with specific inhibitor or siRNA augmented MH-induced apoptotic cell death. 4-O-methylhonokiol inhibited tumor growth, NF-κB activity and expression of antiapoptotic proteins; however, it increased the expression of apoptotic proteins as well as p21 in xenograft nude mice bearing SW620 cancer cells. The present study reveals that MH causes p21-mediated human colon cancer cell growth inhibition through suppression of NF-κB and indicates that this compound by itself or in combination with other anticancer agents could be useful for the treatment of cancer.
    The Journal of nutritional biochemistry 08/2011; 23(7):706-15. DOI:10.1016/j.jnutbio.2011.03.013 · 3.79 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Oxidative stress induced neuronal cell death by accumulation of β-amyloid (Aβ) is a critical pathological mechanism of Alzheimer's disease (AD). Intracerebroventrical infusion of Aβ1-42 (300 pmol/day per mouse) for 14 days induced neuronal cell death and memory impairment, but pre-treatment of 4-O-methylhonokiol (4-O-MH), a novel compound extracted from Magnolia officinalis for 3 weeks (0.2, 0.5 and 1.0 mg/kg) prior to the infusion of Aβ1-42 and during the infusion dose dependently improved Aβ1-42-induced memory impairment and prevented neuronal cell death. Additionally, 4-O-MH reduced Aβ1-42 infusion-induced oxidative damages of protein and lipid but reduced glutathione levels in the cortex and hippocampus. Aβ1-42 infusion-induced activation of astrocytes and p38 mitogenic activated protein (MAP) kinase was also prevented by 4-O-MH in mice brains. In further study using culture cortical neurons, p38 MAP kinase inhibitor abolished the inhibitory effect of 4-O-MH (10 μM) on the Aβ1-42 (5 μM)-induced reactive oxidative species generation and neuronal cell death. These results suggest that 4-O-MH might prevent the development and progression of AD through the reduction of oxidative stress and neuronal cell death via inactivation of p38 MAP kinase pathway.
    The Journal of nutritional biochemistry 05/2011; 22(5):476-486. DOI:10.1016/j.jnutbio.2010.04.002 · 3.79 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Several studies have shown physiological functions of interleukin (IL)-32, a novel cytokine. However, the role of IL-32 in cancer development has not been reported. In this study, we showed that IL-32γ inhibited tumor growth in IL-32γ-overexpressing transgenic mice inoculated with melanoma as well as colon tumor growth in xenograft nude mice inoculated with IL-32γ-transfected colon cancer cells (SW620). The inhibitory effect of IL-32γ on tumor growth was associated with the inhibition of constitutive activated nuclear transcription factor-κB (NF-κB) and of signal transducer and activator of transcription 3 (STAT3). The expression of antiapoptotic, cell proliferation and tumor-promoting genes (bcl-2, X-chromosome inhibitor of apoptosis protein (IAP), cellular IAP and cellular FADD-like IL-1β-converting enzyme-inhibitory protein, cyclin D), cyclin-dependent kinase 4, cycolooxygenase-2 and inducible nitric oxide synthase was decreased, whereas the expression of apoptotic target genes (caspase-3 and -9, bax) increased. In tumor, spleen and blood, the number of cytotoxic CD8(+) T cells and CD57(+) natural killer cells and the levels of IL-10 increased, but that of tumor necrosis factor-α (TNF-α), IL-1β and IL-6 decreased. We also found that forced overexpression of IL-32γ inhibited colon cancer cell (SW620 and HCT116) growth accompanied with the inhibition of activated NF-κB and STAT3 in vitro. In addition, when IL-32γ was knocked down by small interfering RNA (siRNA) or neutralized with an anti-IL-32γ antibody, IL-32γ-induced colon cancer cell growth inhibition, the IL-32γ-induced decrease of TNF-α, IL-1 and IL-6 production, and the increase of IL-10 production were abolished. However, siRNA of NF-κB and STAT3 augmented IL-32γ-induced colon cancer cell growth inhibition. These findings indicate significant pathophysiological roles of IL-32γ in cancer development.
    Oncogene 03/2011; 30(30):3345-59. DOI:10.1038/onc.2011.52 · 8.46 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The bioactive constituents isolated from the bark of Magnolia officinalis such as magnolol, honokiol and obovatol have anti-inflammatory properties through the inactivation of NF-κB which is an important factor in the regulation of inflammatory reaction. We recently isolated a novel neolignan compound, 4-O-methylhonokiol, from M. officinalis. In the present study, we investigated whether or not 4-O-methylhonokiol inhibits inflammatory reaction through the inhibition of NF-κB activity. The results showed that 4-O-methylhonokiol (2.5–10 μM) inhibited LPS (1 μg/ml)-induced NO generation in macrophage Raw 264.7 cells in a concentration-dependent manner with IC50 value 9.8 μM. The inhibition of NO generation by 4-O-methylhonokiol was consistent with the inhibitory effect on the expression as well as transcriptional activity of inducible nitric oxide synthase (iNOS). In addition, 4-O-methylhonokiol inhibited the LPS-induced transcriptional and DNA binding activities of NF-κB as well as p50 and p65 translocation into the nucleus. Topical application of 4-O-methylhonokiol (0.1–1 mg/ear) inhibited 12-O-tetradecanoylphorbol-13-acetate-induced inflammatory ear edema formation, NF-κB activity, and iNOS and COX-2 expression. The present results provided evidence that 4-O-methylhonokiol has anti-inflammatory properties through inhibition of the NF-κB pathway, and suggested that 4-O-methylhonokiol can be used as an anti-inflammatory agent.
    Chemico-Biological Interactions 12/2010; 188(3):677-677. DOI:10.1016/j.cbi.2010.08.006 · 2.58 Impact Factor

Publication Stats

551 Citations
119.47 Total Impact Points


  • 2007-2015
    • Chungbuk National University
      • College of Pharmacy
      Chinsen, Chungcheongbuk-do, South Korea
  • 2012
    • Konkuk University
      • Department of Bioscience and Technology
      Sŏul, Seoul, South Korea