• BMB Reports
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• v.39 no.2
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• pp.171-177
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• 2006

Nonsteroidal anti-inflammatory drugs such as indomethacin (IN) can exert anti-colorectal cancer (CRC) activity through cyclooxygenase independent mechanism, but the exactly biological mechanism is not completely known. Here we use proteomic tools to investigate the molecular mechanism of this action. First, nude mice bearing tumors derived from subcutaneous injection with human CRC cell line HCT116 were randomly allocated to groups treated with or without indomethacin. Later, tumor lumps were incised and then total proteins extracted. After separated with two-dimensional electrophoresis, thirty-one differently expressed spots were found between IN-treated and non-IN-treated groups, of which 25 spots decreased and 6 spots increased in abundance in IN-treated group. Through matrix-assisted laser desorption ionization time of flight mass spectrometry and then NCBInr and SWISS-PROT databases searching, 12 protein spots were finally identified including galectin-1, annexin A1, annexin IV, trancription factor BTF3A, calreticulin. Most of the identified proteins are correlated with tumor's biological prosperities of proliferation, invasion, apoptosis and immunity, or take part in cell's signal transduction. From above we thought that indomethacin can exert its effect on colorectal cancer through regulating several proteins' expression directly or indirectly. Further study of these proteins may be helpful in founding new targets of drugs for cancer chemotherapy.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.10015-10020
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• 2014

Background: Fentanyl is used as an analgesic to treat pain in a variety of patients with cancer and recently it has become considered to also act as an antitumor agent. The study present was designed to investigate the effects of fentanyl on colorectal cancer cell growth and plausible mechanisms. Materials and Methods: The human colorectal carcinoma cell line HCT116 was subcutaneously injected into nude mice. The viability of HCT116 was tested by MTT assay, and apoptosis by flow cytometry and caspase-3 activity. The expression of Sirt1 and NF-${\kappa}B$ were evaluated by Western blotting and the levels of Sirt1 and NF-${\kappa}B$ by fluorescence method. SiRNA was used to silence and Ad-Sirt1 to overexpress Sirt1. Results: Our data showed that fentanyl could inhibit tumor growth, with increased expression of Sirt1 and down-regulation of Ac-p65 in tumors. Compared with control cells without treatment, HCT116 cells that were incubated with fentanyl had a higher apoptotic rate. Moreover, fentanyl could increase expression and activity of Sirt1 and inhibitor expression and activity of NF-${\kappa}B$, which might be mechanisms of fentanyl action. Conclusions: Fentanyl increased colorectal carcinoma cell apoptosis by inhibition of NF-${\kappa}B$ activation in a Sirt1-dependent manner.

• Journal of the Korea Convergence Society
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• v.9 no.6
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• pp.147-154
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• 2018

The purpose of this study is to clarify the structure of healing coded through transcriptional activity in the poem of Cho Ji-Hoon in the aspect of literary therapy. In particular, the search for how the codes of emotion are activated through neurophysiologic synapse. The variation of emotional codes developed in Cho Ji-Hoon's poem is in line with the encoding of literary therapy. Emotions emanating from poetic statements stimulate the transition of new emotions and activate emotions of healing. Cho Ji-Hoon's poem fuses emotions through the floods of various poetic transitions. It is then forming an overall healing forest. The healing content is discussed by the structure of transition, and all the structures are linked to the contents of healing. It is a greater part of sad lyricism by the action of descent and ascension, and green aesthetics of the leaves. In the future, if Cho Ji-Hoon's research on poetry is activated, we will be able to meet genuine stories about his natural and literary healing life.

• The Journal of Korean Society of Virology
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• v.27 no.1
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• pp.69-75
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• 1997

To evaluate in vitro anti-HIV efficacies of nucleoside derivatives, MT-4 cell line was infected with HIV-1 and HIV-2 respectively and treated with various compounds and the formerly approved drugs such as AZT, d4T, ddC and ddI. CPE method was used to evaluate their antiviral activity. Most dideoxynucleosides, AZT, d4T, ddC and ddI, showed anti-HIV activities against both viruses but no other compounds including anti-herpesvirus drugs did any. Further experiments were carried out to study their inhibitory mechanism of viral adsorption. The results showed no inhibition of syncytium formation due to an interaction between the gp120 expressed in HIV -infected cell surface and CD4 receptor on the uninfected cell surface in the presence of AZT. AZT showed no activity up to $100\;{\mu}g/ml$. Inhibition of reverse transcriptase (RT) in the presence of AZT-triphosphate was tested by using RT expressed in E. coli and purified and its $IC_{50}$ was 4.5 nM.

• Molecules and Cells
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• v.43 no.7
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• pp.662-670
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• 2020

We have investigated the involvement of the pre-mRNA processing factor 4B (PRP4) kinase domain in mediating drug resistance. HCT116 cells were treated with curcumin, and apoptosis was assessed based on flow cytometry and the generation of reactive oxygen species (ROS). Cells were then transfected with PRP4 or pre-mRNA-processing-splicing factor 8 (PRP8), and drug resistance was analyzed both in vitro and in vivo. Furthermore, we deleted the kinase domain in PRP4 using Gateway™ technology. Curcumin induced cell death through the production of ROS and decreased the activation of survival signals, but PRP4 overexpression reversed the curcumin-induced oxidative stress and apoptosis. PRP8 failed to reverse the curcumin-induced apoptosis in the HCT116 colon cancer cell line. In xenograft mouse model experiments, curcumin effectively reduced tumour size whereas PRP4 conferred resistance to curcumin, which was evident from increasing tumour size, while PRP8 failed to regulate the curcumin action. PRP4 overexpression altered the morphology, rearranged the actin cytoskeleton, triggered epithelial-mesenchymal transition (EMT), and decreased the invasiveness of HCT116 cells. The loss of E-cadherin, a hallmark of EMT, was observed in HCT116 cells overexpressing PRP4. Moreover, we observed that the EMT-inducing potential of PRP4 was aborted after the deletion of its kinase domain. Collectively, our investigations suggest that the PRP4 kinase domain is responsible for promoting drug resistance to curcumin by inducing EMT. Further evaluation of PRP4-induced inhibition of cell death and PRP4 kinase domain interactions with various other proteins might lead to the development of novel approaches for overcoming drug resistance in patients with colon cancer.

• The Korea Journal of Herbology
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• v.28 no.1
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• pp.33-42
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• 2013

Objective : Morus alba Linne Root Bark (MRAL) is a medicinal herb in Korean Medicine, known for its anti-inflammatory and anti-allergic properties. However, its mechanisms of action and the cellular targets have not yet been found and the study was developed to investigate the allergic suppressive effect of MRAL. The purpose of this study is to investigate the allergic suppressive effects of MRAL on activation of MC/9 mast cells. Methods : Cytotoxic activity of MRAL (50, 100, 200, 400 ${\mu}g/mL$) on MC/9 mast cells measured using EZ-Cytox cell viability assay kit (WST reagent). The levels of interleukin-5 (IL-5), IL-13 and IL-4, IL-5, IL-6, IL-13 mRNA expression were measured by enzyme-linked immunosorbent assay (ELISA) and real-time PCR respectively. The expression of transcription factors such as GATA-1, GATA-2, NFAT, AP-1 and NF-${\kappa}B$ p65 DNA binding activity were measured by western blot and electrophoresis mobility shift assay (EMSA). Results : Our results indicated that MRAL (50 ${\mu}g/mL$, 100 ${\mu}g/mL$) significantly inhibited PMA/Ionomycin-induced production of IL-5 and IL-13 and the expression of IL-4, IL-5, IL-6 and IL-13 mRNA in MC/9 mast cells. Moreover, MRAL (50 ${\mu}g/mL$, 100 ${\mu}g/mL$) inhibited PMA/Ionomycin-induced GATA-1, GATA-2, NFAT-1, NFAT-2, c-Fos protein expression and NF-${\kappa}B$ p65 DNA binding activity in MC/9 mast cells. Conclusions : In conclusion, we suspect the anti-allergenic activities of MRAL, may be related to the regulation of transcription factors GATA-1, GATA-2, NFAT-1, NFAT-2, c-Fos and NF-${\kappa}B$ p65 DNA binding assay causing inhibition of Th2 cytokines IL-5 and IL-13 in mast cells.

• Biomolecules & Therapeutics
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• v.15 no.2
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• pp.95-101
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• 2007

Resveratrol (3,5,4’-trihydroxy-trans-stilbene), a naturally occurring phytoallexin abundant in grapes and several plants, has been shown to be active in inhibiting proliferation and inducing apoptosis in several human cancer cell lines. On the line of the biological activity of resveratrol, a variety of resveratrol analogs were synthesized and evaluated for their growth inhibitory effects against several human cancer cell lines. In the present study, we found that one of the resveratrol analogs, 3,4,5-trimethoxy-4’-bromo-cis-stilbene, markedly suppressed human colon cancer cell proliferation (EC$_{50}$ = 0.01 ${\mu}$g/ml), and the inhibitory activity was superior to its corresponding trans-isomer (EC$_{50}$ = 1.6 ${\mu}$g/ml) and resveratrol (EC$_{50}$ = 18.7 ${\mu}$g/ml). Prompted by the strong growth inhibitory activity in cultured human colon cancer cells (Col2), we investigated its mechanism of action. 3,4,5-Trimethoxy-4’-bromo-cis-stilbene induced arrest of cell cycle progression at G2/M phase and increased at sub-G1 phase DNA contents of the cell cycle in a time- and dose-dependent manner. Colony formation was also inhibited in a dose-dependent manner, indicating the inhibitory activity of the compound on cell proliferation. Moreover, the morphological changes and condensation of the cellular DNA by the treatment of the compound were well correlated with the induction of apoptosis. These data suggest the potential of 3,4,5-trimethoxy-4’-bromo-cis-stilbene might serve as a cancer chemotherapeutic or chemopreventive agent by virtue of arresting the cell cycle and inducing apoptosis for the human colon cancer cells.

• The Korean Journal of Physiology and Pharmacology
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• v.11 no.2
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• pp.37-43
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• 2007

Adenosine has been reported to provide cytoprotection in the central nervous systems as well as myocardium by activating cell surface adenosine receptors. However, the exact target and mechanism of its action still remain controversial. The present study was performed to examine whether adenosine has a protective effect against $A{\beta}$-induced injury in neuroglial cells. The astrocyte-derived human neuroglioma cell line, A172 cells, and $A{\beta}_{25{\sim}35}$ were employed to produce an experimental $A{\beta}$-induced glial cell injury model. Adenosine significantly prevented $A{\beta}$-induced apoptotic cell death. Studies using various nucleotide receptor agonists and antagonists suggested that the protection was mediated by $A_1$ receptors. Adenosine attenuated $A{\beta}$-induced impairment in mitochondrial functional integrity as estimated by cellular ATP level and MTT reduction ability. In addition, adenosine prevented $A{\beta}$-induced mitochondrial permeability transition, release of cytochrome c into cytosol and subsequent activation of caspase-9. The protective effect of adenosine disappeared when cells were pretreated with 5-hydroxydecanoate, a selective blocker of the mitochondrial ATP-sensitive $K^+$ channel. In conclusion, therefore we suggest that adenosine exerts protective effect against $A{\beta}$-induced cell death of A172 cells, and that the underlying mechanism of the protection may be attributed to preservation of mitochonarial functional integrity through opening of the mitochondrial ATP-sensitive $K^+$ channels.

• Archives of Pharmacal Research
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• v.27 no.9
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• pp.893-900
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• 2004

2- or 6-Substituted BZT-N derivatives were synthesized, and their cytotoxic activity against can-cer L1210 and SNU-1 cells was examined. The antitumor action was also assessed in mice bearing S-180 cells in peritoneal cavity. In a comparison, it was found that 6-substituted BZT-N derivatives exhibited higher potencies in both bioactivities than 2-substituted BZT-N derivatives against L1210 cells in in vitro and S-180 in vitro tests exception of compound 36. Interestingly, it was observed that 2-substituted compound 36, which has methyl group at RI position, exhib-ited a better antitumor activity than 6-substituted compounds against L1210 and SNU-1 in vitro. The EDso value of 2-substituted compound 36 against L1210 was found to be comparable to the EDso value of adriamycin and was even better against the solid cancer cell line SNU-1. It was also observed that 2-substituted compound 36 showed better antitumor activity in mice bearing S-180 cells in the peritoneal cavity. The T/C (％) value of 2-substituted compound 36 was simi-lar to that of adriamycin. Quantitative structure-activity relationship (QSAR) tests reveal that the experimental E $D_{50}$ values against SNU-1 closely correlate with both the calculated HOMO ener-gies ( $E_{HOMO}$) and the measured H-NMR chemical shift of 3-H ($\delta$$_{H}$). The results suggests that a compound having higher $E_{HOMO}$ and $\delta$$_{H}$ values usually should have a lower E $D_{50}$ (SNU-1) value.lue.lue.lue.

• Korean Journal of Plant Resources
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• v.25 no.2
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• pp.169-175
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• 2012

For the elucidation of action mechanism on anti-HIV of natural resources, the extracts of $Campsis$ $grandiflora$ were tested for their inhibitory effects on HIV-1 replication and its essential enzymes as the reverse transcriptase (RT), protease and ${\alpha}$-glucosidase. In the assay of HIV-1-infected human T-cell line, water extracts of stem inhibited the HIV-1-induced cytopathic effects with IC (inhibitory concentration) of 100 ${\mu}g$/ml. Moreover water extracts (100 ${\mu}g$/ml) of stem showed strong activity of 37.9% on anti-HIV-1 RT using Enzyme Linked Oligonucleotide Sorbent Assay (ELOSA) method. In the HIV-1 protease inhibition assay, methanol extracts of stem and leaf extract showed 33.6% and 31.5% inhibition of the enzyme activity to cleave an oligopeptide resembling one of the cleavage sites in the viral polyprotein which can only be processed by HIV-1 protease, but did not exhibited glucosidase inhibitory activities. From these results, it is suggested that the inhibition of the viral replication $in$ $vitro$ is due to the inhibition of reverse transcriptase by water extracts of stem of $Campsis$ $grandiflora$.