• Tuberculosis and Respiratory Diseases
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• v.45 no.3
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• pp.587-595
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• 1998

Background: Recombinant adenovirus hold promise as vectors to carry therapeutic genes for several reasons: 1) they can infect both dividing and non-dividing cells; 2) they have the ability to directly transduce tissues in vivo; 3) they can easily be produced in high titer; and 4) they have an established record of safety as vaccination material. However, one of the major limitation in the use of adenoviruses is that transgene expression is quite short because adenovirusees insert their DNA genome episomally rather than by chromosomal integration, and an immune response against the virus destroys cells expressing the therapeutic gene. Since sodium butyrate has been reported to induce adenovirus-mediated gene expression, we hypothesized that treatment of tumor cells, transduced with herpes simples virus thymidine kinase(HSVtk) gene using adenoviral vector, with butyrate could augment the effect of gene therapy. Methods: We transduced HSVtk gene, driven by the cytomegalovirus promoter, into REN cell line(human mesothelioma cell line). Before proceeding with the comparison of HSVtk/ganciclovir mediated bystander killing, we evaluated the effect of butyrate on the growth of tumor cells in order to rule out a potential antitumor effect of butyrate alone, and also on expression of HSVtk gene by Western blot analysis. Then we determined the effects of butyrate on bystander-mediated cell killing in vitro. Results: There was no inhibition of growth of cells exposed to butyrate for 24 hours at a concentration of 1.5mM/L. Toxic effects were seen when the concentration of butyrate was greater than 2.0mM/L. Gene expression was more stable and bystander effect was augmented by butyrate treatment of a concentration of 1.5mM/L. Conclusion: These results provide evidence that butyrate can augment the efficiency of cell killing with HSVtk/GCV system by inducing transgene expression and may thus by a promising new approach to improve responses in gene therapy using adenoviral vectors.

• Journal of Life Science
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• v.17 no.10
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• pp.1447-1451
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• 2007

Through the screening of marine natural compounds that inhibit cancer cell proliferation, we previously reported that pectenotoxin-2 (PTX-2) isolated from marine sponges exhibits selective cytotoxicity against several cell lines in p53-deficient tumor cells compared to those with functional p53. However, the molecular mechanisms of its anti-proliferative action on malignant cell growth are not completely known. To further explore the mechanisms of its anti-cancer activity and to test whether the status of p53 in liver cancer cells correlates with their chemo-sensitivities to PTX-2, we used two well-known hepatocarcinoma cell lines, p53-deficient Hep3B and p53-wild type HepG2. We have demonstrated that PTX-2 markedly inhibits Hep3B cell growth and induces apoptosis whereas HepG2 cells are much more resistant to PTX-2 suggesting that PTX-2 seems to act by p53-independent cytotoxic mechanism. The apoptosis induced by PTX-2 in Hep3B cells was associated with the modulation of DNA fragmentation factor (DFF) family proteins, up-regulation of pro-apoptotic Bcl-2 family members such as Bax and Bcl-xS and activation of caspases (caspase-3, -8 and -9). Blockade of the caspase-3 activity by caspase-3 inhibitor, z-DEVD-fmk, prevented the PTX-2-induced growth inhibition in Hep3B cells. Moreover, treatment with PTX-2 also induced phosphorylation of AKT and extracellular-signal regulating kinase (ERK), but not c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MARK). Specific inhibitors of PI3K inhibitor (LY294002) and ERK1/2 inhibitor (PD98059) significantly blocks PTX-2-induced-anti-proliferative effects, whereas a JNK inhibitor (SP600125) and a p38 MAPK inhibitor (SB203580) have no significant effects demonstrating that the pro-apoptotic effect of PTX-2 mediated through activation of AKT and ERK signal pathway in Hep3B cells.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6327-6332
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• 2012

Esophageal cancer is a common malignant tumor occurring in human esophageal epithelial tissue. The primary purpose of this paper was to define the effects of ${\beta}$-carotene and 1,25-dihydroxyvitamin $D_3$, alone and in combination, on cell proliferation, cell cycle and apoptosis of human esophageal cancer EC9706 cells. Treatment with different concentrations of ${\beta}$-carotene and/or 1,25-dihydroxyvitamin $D_3$. MTT assay showed that ${\beta}$-carotene and 1,25-dihydroxyvitamin $D_3$ significantly inhibited proliferation of EC9706 cells in a dose- and time-dependent manner. Further studies also demonstrated that ${\beta}$-carotene alone or 1,25-dihydroxyvitamin $D_3$ alone caused a marked increase on the induction of apoptosis in EC9706 cells. The percentage of G0/G1-phase cells significantly increased on addition of 1,25-dihydroxyvitamin $D_3$ alone, but there were no significant changes with ${\beta}$-carotene alone. These two agents in combination synergistically inhibited cell growth and induced apoptosis. Therefore, our results indicate that ${\beta}$-carotene and 1,25-dihydroxyvitamin $D_3$ in combination may provide a novel strategy for preventing and treating esophageal cancer.

• Journal of the Korean Society of Food Science and Nutrition
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• v.21 no.5
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• pp.544-550
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• 1992

This study was investigated on the antitumor effects of protein-polysaccharide fraction(PPF) extracted from seaweeds such as sea-lettuce and gonpi toward sarcoma-180 cells. In the PPF extracted from these seaweeds, the polysaccharide contents of sea-lettrce and gonpi were 52.20% and 48.16%, respectively. The highest levels of constituents monosaccharides found in seaweeds was fructose. The major amino acids were aspartic acid, glutamic acid, glycine and cystein. The solid tumor growth inhibition showed the highest level of 64.55% when 50mg/kg sea-lettuce was administerated. The life prolongation effect was 18.31% at 50mg/kg of gonpi. In the effects of immunologic activity, when 50mg/kg sea-lettuce was administrated, the number of circulating leucocyte showed the highest level (65.11%). The number of total peritoneal exudate cells of the sea-lettuce administerated group was increased significantly in comparison with the control group. The hematological analysis of the experimental group was similar with that of the control group.

• Journal of Life Science
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• v.18 no.6
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• pp.804-813
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• 2008

Cordyceps militaris, the Chinese medicinal fungal genus Cordyceps, is reported to possess many pharmacological activities including immunological stimulating, anti-cancer, anti-virus and anti-infection activities. However, the molecular mechanisms of C. militaris on biochemical actions in cancer have not been clearly elucidated yet. In the present study, we investigated the anti-proliferative activity of the water extract of C. militaris (WECM) in human hepatocellular carcinoma HepG2 cells. It was found that WECM could inhibit the cell growth in a dose-dependent manner, which was associated with morphological changes and apoptotic cell death such as formation of apoptotic bodies and increased populations of apoptotic sub-G1 phase. Apoptotic cell death of HepG2 cells by WECM was connected with a up-regulation of pro-apoptotic Bax expression, tumor suppressor p53 and cyclin-dependent kinase inhibitor p21 (WAF1/CIP1). In addition, WECM treatment induced the proteolytic activation of caspase-3 and a concomitant degradation and/or inhibition of poly (ADP-ribose) polymerase (PARP), ${\beta}-catenin$ and phospholipase $(PLC)-{\gamma}1$ protein. Furthermore, caspase-3 inhibitor, z-DEVD-fmk, significantly inhibited WECM-induced apoptosis demonstrating the important role of caspase-3 in the observed cytotoxic effect. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of C. militaris.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2023.04a
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• pp.50-50
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• 2023

Prostaglandin E2(PGE2), a major product of cyclooxygenase-2 (COX-2), plays an important role in the carcinogenesis of many solid tumors, including colorectal cancer. Because PGE2 functions by signaling through PGE2 receptors (Eps), which regulate tumor cell growth, invasion, and migration, there has been a growing amount of interest in the therapeutic potential of targeting Eps. In the present study, we investigated the role of EP4 on the effectiveness of cordycepin in inhibititing the migration and invasion of HCT116 human colorectal carcinoma cells. Our data indicate that cordycepin suppressed lipopolysaccharide (LPS)-enhanced cell migration and invasion through the inactivation of matrix metalloproteinases (MMP)-9 as well as the down-regulation of COX-2 expression and PGE2 production. These events were shown to be associated with the inactivation of EP4 and activation of AMP-activated protein kinase (AMPK). Moreover, the AMPK inhibitor, compound C, as well as AMPK knockdown via siRNA, attenuated the cordycepin-induced inhibition of EP4 expression. Cordycepin treatment also reduced the activation of CREB. These findings indicate that cordycepin suppresses the migration and invasion of HCT116 cells. Through modulating EP4 expression and the AMPK-CREB signaling pathway. Therefore, cordycepin has the potential to serve as a potent anti-cancer agent in therapeutic strategies against colorectal cancer metastasis.

• Journal of Life Science
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• v.17 no.9 s.89
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• pp.1191-1196
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• 2007

Eugenol (4-allyl-2-methoxyphenol) is a main component of essential oils obtained from various spices. Recent reports have shown that eugenol induces growth inhibition and apoptosis of malignant tumor cells. In this study, the stimulatory effect of eugenol on cell differentiation was investigated in HL-60 promyelocytic leukemia cells. When HL-60 cells were treated in combination with 150 ${\mu}M$ of eugenol and 3 nM of $1{\alpha},25-dihydroxyvitamin$ $D_{3}$, cell growth was slower than that of cells treated with eugenol or $1{\alpha},25-dihydroxyvitamin$ $D_{3}$ alone. Eugenol enhanced low dose of $1{\alpha,25-dihydroxyvitamin }$ $D_{3}-induced$ a $G_{0}/G_{1}$ phase arrest in cell cycle. Consistent with this, combined treatment of eugenol and $1{\alpha},25-dihydroxyvitamin$ $D_{3}$ cooperatively increased p27 level and decreased cyclin A, cdk 2 and cdk 4 levels, which are cell cycle regulators related to $G_{0}/G_{1}$ arrest. According to flow cytometric analysis, the expression of CD14 (monocytic differentiation marker) was more increased in the cells co-treated with eugenol and $1{\alpha},25-dihydroxyvitamin$ $D_{3}$. These results indicate that eugenol potentiates cell differentiation mediated by $1{\alpha},25-dihydroxyvitamin$ $D_{3}$ of suboptimal concentration. The differentiation-inducing property of eugenol maybe contributes to chemopreventive activity of cancer.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.7
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• pp.975-982
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• 2015

Piceatannol (trans-3,4,3',5'-trihydroxystilbene), a natural stilbene, is an analogue of resveratrol. In the present study, possible mechanisms by which piceatannol exerts its pro-apoptotic action in cultured human oral cancer YD-15 cells were investigated. To investigate whether or not piceatannol has effects on cancer cell viability, human oral YD-15 cells were treated with piceatannol (0, 50, and $100{\mu}M$). Piceatannol treatment ($100{\mu}M$) showed the strongest inhibition of cell proliferation and reduced cell viability in a dose-dependent manner. Chromatin condensation detected by DAPI staining significantly increased in a concentration-dependent manner, indicating apoptosis. Piceatannol treatment activated initiator Bax (pro-apoptotic) and cPARP in a concentration-dependent manner. Further, piceatannol induced down-regulation of Bcl-2 (anti-apoptotic). We also evaluated the activity of piceatannol against oral cavity cancer tumors in mice. Piceatannol-treated nude mice bearing YD-15 xenograft tumors exhibited significantly reduced tumor volume and weight due to the potent effect of piceatannol on tumor cell apoptosis, as determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. Immunohistochemistry staining showed elevated expression of cleaved-caspase-3 as well as reduced expression of Ki-67 in the piceatannol-treated group. Therefore, piceatannol can be developed as a cancer preventive medicine due to its growth inhibitory effects and induction of apoptosis in human oral cancer cells.

• Biomolecules & Therapeutics
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• v.12 no.4
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• pp.221-227
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• 2004

Nonsteroidal anti-inflammatory drugs (NSAIDs), particularly the highly selective cyclooxygenase (COX)-2 inhibitors have been shown to decrease the growth of tumor, in part, by inhibition of neovascularization. Recently, besides mature endothelial cells, endothelial progenitor cells (EPCs) have been shown to contribute neovascularization in angiogenic tissues. In this study, we addressed a question whether nimesulide, a selective COX-2 inhibitor, could affect differentiation of EPCs into adhesive endothelial cells in vitro. Total mononuclear cells were isolated from cord blood by Ficoll density gradient centrifugation, and then the cells were incubated with nimesulide or vehicle control for 7 days. The number of adherent and spindle-shaped cells decreased by nimesulide treatment in a concentration-dependent fashion at a concentration range of 5 - 200 ${\mu}M$. Moreover, the adherent cells double positive for DiI-ac-LDL uptake and lectin binding significantly decreased upon nimesulide treatment. There was no change of expression of CD31 between treatment and control groups, whereas slight reduction was detected upon treatment in expression of VE-cadherin, ICAM-1, vWF, ${\alpha}v$, and ${\alpha}5$. Nimesulide also reduced cell viability during first 3 days' culture and induced apoptosis in adherent EPCs, resulting in increased annexin-V-positive and propidium iodide-negative cells. Taken together, these results suggest that nimesulide could be applied for the inhibition of new vessel formation, in part, by inhibiting differentiation and survival of EPCs.

• Food Science and Preservation
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• v.22 no.1
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• pp.19-26
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• 2015

Indole 3-carbinol (I3C), important component of cruciferous vegetables and its major acid-catalyzed metabolite, 3,3'-diindolylmethane (DIM) have been suggested to have an inhibitory effect on the tumor growth and metastasis. This study investigated the effect of DIM on the adhesion, migration and invasion of highly invasive PC3 and DU145 human prostate cancer cell lines. Cells were grown in Dulbecco's modified Eagle's medium (DMEM) supplemented with 3.0 g/L glucose, 3.7 g/L sodium bicarbonate and 10% fetal bovine and were incubated in a humidified incubator at $37^{\circ}C$ and 5% $CO_2$. DIM reduced the adhesion of PC3 and DU145 cells in a dose dependent manner. The pretreatment of PC3 cells with DIM reduced the adhesion dose dependantly, but inhibition was less effective than the treatment with DIM during the adhesion assay. The migration and invasion of PC3 and DU145 cells were reduced by DIM dose dependantly, and the inhibition of DIM was less effective in the DU145 cells than in the PC3 cells. The pretreatment of PC3 cells with DIM for 24 hr before the assay reduced invasion of PC3 cells by 37%. These results suggest that DIM inhibits adhesion, migration and invasion of the PC3 and DU145 cells and may be an effective antimetastatic therapy in addition to traditional chemotherapy.