• Title, Summary, Keyword: celecoxib

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Effects of a Selective COX-2 Inhibitor Celecoxib and Soy-Isoflavones on Molecular Markers Related to Apoptosis, and COX-2 and Mapkinase Expression in Estrogen-Fed Rats

  • Kim, Tae-Kyung;Park, Ock Jin
    • Nutritional Sciences
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    • v.8 no.1
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    • pp.16-22
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    • 2005
  • The present study examined the effects of cyclooxygenase-2 (COX-2) inhibitor celecoxib or soy-isoflavones in the presence of estrogen on apoptosis related gene expression, COX-2 and mapkinase in 48-week old female rats. Expressions of bel-2 and bax proteins, which are known to be involved in the regulation of apoptosis, were investigated in mammary glands and heart tissues. The elevated expression of bel-2 expression was observed in mammary glands of celecoxib supplemented rats as well as soy-isoflavones. The mammary glands bel-2/bax ratio was found to be higher in celecoxib or soy-isoflavones supplemented rats. However, in heart tissues, expression of bel-2 and bax was in the order of control, celecoxib and soy-isoflavones. The up-regulation of COX-2 was observed in celecoxib or soy-isoflavones in mammary glands. 'The similar trend was not displayed with the mapkinase expression. In heart tissues, the down-regulation of COX-2 as well as mapkinase was observed in celecoxib or soy-isoflavones supplemented rats. Soy-isoflavones and celecoxib both had a similar regulatory pattern of bel-2, bax and COX-2 in mammary glands, and in heart tissues, only COX-2 exhibited a similar down-regulatory properly. These findings revealed that in estrogen sufficient state, celecoxib and soy-isoflavones might not exhibit proapoptotic potential or COX-2 inhibition in normal mammary glands.

Inhibitory Effect of IFN-$\beta$, on the Antitumor Activity of Celecoxib in U87 Glioma Model

  • Kim, Eun-Kyoung;Chung, Dong-Sup;Shin, Hye-Jin;Hong, Yong-Kil
    • Journal of Korean Neurosurgical Society
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    • v.46 no.6
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    • pp.552-557
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    • 2009
  • Objective : Interferon-$\beta$, (IFN-$\beta$) has been used in the treatment of cancers. Inhibition of the enzyme cyclooxygenase (COX) with celecoxib had a significantly suppressive effect on tumor growth, angiogenesis, and metastasis in a variety of tumors. The aim of this study was to elucidate the antiglioma effect of combined treatment with IFN-$\beta$ and celecoxib in U87 glioma model. Methods : The in vitro effects of IFN-$\beta$ (50-1,000 IU/mL) and celecoxib ($50-250\;{\mu}M$) alone or combination of both on the proliferation and apoptosis of U87 cells were tested using MTT assay, FACS analysis and DNA condensation. To determine the in vivo effect, nude mice bearing intracerebral U87 xenograft inoculation were treated with IFN-$\beta$ intraperitoneally ($2{\times}10^5\;IU/day$ for 15 days), celecoxib orally (5, 10 mg/kg) or their combination. Results : IFN-$\beta$ or celecoxib showed an inhibitory effect on the proliferation of U87 cells. When U87 cells were treated with IFN-$\beta$ and celecoxib combination, it seemed that IFN-$\beta$ interrupted the antiproliferative and apoptotic activity of celecoxib. No additive effect was observed on the survival of the tumor bearing mice by the combination of IFN-$\beta$ and celecoxib. Conclusion : These results suggest that IFN-$\beta$ seems to inhibit the antiglioma effect of celecoxib, therefore combination of IFN-$\beta$ and celecoxib may be undesirable in the treatment of glioma.

Effect of Cyclooxygenase-2 Specific Inhibitor (SC-58635) on the Production of Nitric Oxide and Prostaglandin E2 in Lipopolysaccharide-stimulated Macrophage Cells (Cyclooxygenase-2 Specific Inhibitor (SC-58635)가 Lipopolysaccharide로 자극한 대식세포에서 Nitric Oxide와 Prostaglandin E2 생산에 미치는 영향)

  • Hong, Seung-Jae;Yang, Hyung-In;Yoon, Hwi-Joong;Lee, Myoung-Soo;Kang, Hyo-Jong;Kim, Wan-Uk;Lee, Sang-Heon;Cho, Chul-Soo;Kim, Ho-Youn
    • IMMUNE NETWORK
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    • v.3 no.1
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    • pp.69-77
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    • 2003
  • Background: Celecoxib, a COX-2 specific inhibitor, has recently been used for the treatment of rheumatoid arthritis. However, the molecular and cellular mechanisms of celecoxib against RA inflammation remain to be defined. To elucidate the action mechanism of celecoxib on inflammatory cells, we investigated the effect of celecoxib on the production of two important mediators of inflammation, nitric oxide and PGE2 Methods: RAW 264.7 cells stimulated with LPS were preincubated with various concentrations of celecoxib (from $10^{-8}$ to $10^{-5}$ M) and $10{\mu}M$ hydrocortisone, respectively. The production of NO and PGE2, the end products of iNOS and COX-2 genes, were estimated in culture supernatants by Greiss method and EIA, respectively. The expression of iNOS gene, COX-2 gene, $NF-{\kappa}B$, and $I-{\kappa}B$ were determined by RT-PCR and western blot analysis. Results: Celecoxib and hydrocortisone inhibited the production of NO and PGE2 in dose dependent manner, when RAW 264.7 cells were stimulated with LPS. The expression of iNOS was also down-regulated by celecoxib and hydrocortisone. Interestingly, COX-2 gene differentially expressed according to the dose of celecoxib, a decrease with lower dose ($10^{-8}$ M) but an increase with higher dose ($10^{-5}$ M). $NF-{\kappa}B$ binding activity was decreased by lower dose of celecoxib, whereas was not affected by higher dose of it. The expression of $I-{\kappa}B$ was suppressed by higher dose of celecoxib. Conclusion: The celecoxib strongly suppressed the production of NO and PGE2 in LPS-stimulated RAW264.7 cells. The decrease of NO seems to be linked to the inhibition of iNOS by celecoxib. The lower and higher dose of celecoxib differentially regulated the COX-2 expression and $NF-{\kappa}B$ activity.

The Enhancement of Radiosensitivity by Celecoxib, Selective Cyclooxygenase-2 Inhibitor, on Human Cancer Cells Expressing Differential Levels of Cyclooxygenase-2 (선택적 Cyclooxygenase-2 억제제인 Celecoxib가 상이한 Cyclooxygenase-2 발현량을 가진 인간 암세포주들에 대하여 유도하는 방사선 감수성 증진 작용)

  • Pyo Hongryull;Shin You Keun;Kim Hyun Seok;Seong Jinsil;Suh Chang Ok;Kim Gwi Eon
    • Radiation Oncology Journal
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    • v.21 no.3
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    • pp.216-221
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    • 2003
  • Purpose: To investigate the modulation of radiosensitivity by celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, on cancer cells over- and under-expressing COX-2. Materials and Methods: A clonogenic radiation survival analysis was performed on A549 human lung and MCF-7 human breast cancer cell lines incubated in both 1 and $10\%$ fetal bovine serum (FBS) containing media. The apoptosis in both cell lines was measured after treatment with radiation and/or celecoxib. Results: Celecoxib enhanced the radiation sensitivity of the A549 cells in the medium containing the $10\%$ FBS, with radiation enhancement ratios of 1.58 and 1.81 respectively, at surviving fractions of 0.1, with $30\muM\;and\;50\muM$ celecoxib. This enhanced radiosensitivity disappeared in the medium containing the $1\%$ FBS. Celecoxib did not change the radiation sensitivity of the MCF-7 cells in either media. The induction of apoptosis by celecoxib and radiation was not synergistic in either cell line. Conclwsion: Celecoxib, a selective COX-2 inhibitor, preferentially enhanced the effect of radiation on COX-2 over-expressing cancer cells compared to the cells with a low expression, and this effect disappeared on incubation of the cells during drug treatment in the medium with suboptimal serum concentration. Apoptosis did not appear to be the underlying mechanism of this radiation enhancement effect due to celecoxib on the A549 cells. These findings suggest radiosensitization by a selective COX-2 inhibitor is COX-2 dependent.

COX-2 INHIBITOR INDUCED APOPTOSIS IN ORAL SQUAMOUS CELL CARCINOMA CELL LINE THROUGH AKT PATHWAY (COX-2 억제제에 의한 AKT 경로를 통한 구강편평세포암종 세포주의 세포사멸 유도)

  • Seo, Young-Ho;Han, Se-Jin;Lee, Jae-Hoon
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.30 no.1
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    • pp.30-40
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    • 2008
  • The objectives of this study was to check up the effect of celecoxib, COX-2 inhibitor, on the pathogenesis of oral squamous cell carcinoma. After mefenamic acid, aspirin and celecoxib, COX-2 inhibitor, were inoculated to HN 22 cell line, the following results were obtained through tumor cell viability by wortmannin, growth curve of tumor cell line, apoptotic index, PGE2 synthesis, total RNA extraction, RT-PCR analysis and TEM features. 1. When wortmannin and celecoxib were given together, the survival rate of tumor cells was lowest about 47 %. So wortmannin had an effect on the decrease of survival rate of tumor cells. 2. In growth curve, the slowest growth was observed in celecoxib inoculated group. 3. The synthesis of PGE2 was decreased in all group and the obvious suppression and highest apoptotic index was observed in celecoxib inoculated group. 4. Suppression of expression of COX-2 mRNA was evident in celecoxib inoculated group. But that of COX-1,2 mRNA was observed in mefenamic acid inoculated group and aspirin inoculated group. 5. In celecoxib inoculated group, mRNA expression of AKT1 was decreased and that of PTEN & expression of caspase 3 and 9 was evidently increased. Depending on above results, when celecoxib was inoculated to oral squamous cell carcinoma cell line, an increase of mRNA expression of caspase 3,9 and PTEN is related to a decrease of mRNA expression of AKT1. Wortmannin had an effect on the decrease of survival rate of tumor cells. Celecoxib might induce apoptosis of tumor cell by suppression of AKT1 pathway and COX-2 inhibition. This results suggested that COX-2 inhibitor might be significantly effective in chemoprevention of oral squamous cell carcinoma.

Crystal Form of Celecoxib: Preparation, Characterization and Dissolution

  • Jin, Mi-Ryung;Sohn, Young-Taek
    • Journal of the Korean Chemical Society
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    • v.62 no.5
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    • pp.352-357
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    • 2018
  • Celecoxib (4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide) is a cyclooxygenase-2 inhibitor used in the treatment of arthritis, acute pain, and dysmenorrhoea. Celecoxib is a Biopharmaceutics Classification System (BCS) class II compound whose oral bioavailability is highly limited owing to its poor aqueous solubility. Several polymorphs of celecoxib have been identified as Form I, Form II, and Form III with melting points of about $162.8^{\circ}C$, $161.5^{\circ}C$, and $160.8^{\circ}C$, respectively. Form IV was generated from the precipitated suspension in the presence of HPMC (Hydroxypropyl methylcellulose) and Polysorbate 80. A rapid rate of dissolution is useful because the rate of dissolution of a drug typically increases its bioavailability. The aim of this study was to investigate the possibility of production of new crystal form of celecoxib that has higher solubility than Form III. New crystal form of celecoxib (Form A) has been isolated by recrystallization and characterized by differential scanning calorimetry (DSC), thermogravimetric (TG) analysis and powder X-ray diffractometry (PXRD). Form A was dissolved faster than Form III. At 30 minutes, the dissolution of Form A was 97.3%, whereas the dissolution of Form III was 82.2% (p < 0.1). After storage of three months at $20^{\circ}C$, in 24% RH (Relative Humidity), the crystal form was not transformed.

CELECOXIB INHIBITS PHORBOL ESTER-INDUCED PGE$_2$ PRODUCTION AND COX-2 EXPRESSION BY TARGETING OF p38 MAP KINASE AND AP-1 IN MOUSE SKIN

  • Chun, Kyung-Soo;Surh, Young-Joon
    • Proceedings of the Korean Society of Toxicology Conference
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    • pp.175-175
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    • 2002
  • Celecoxib, a selective COX-2 inhibitor, has been reported to prevent experimentally induced colon, breast, bladder, and skin carcinogenesis. Moreover, daily intake of celecoxib resulted in significant reduction of polyps in patients with familial adenomatous polyposis.(omitted)

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Effect of Celecoxib, a Cyclooxygenase-2-specific Inhibitor, has no Effect on Chronically Maintained Neuropathic Pain in Rats (장기간 유지된 신경병증성 통증 흰쥐에서 선택적 COX2 억제제인 Celecoxib의 진통효과)

  • Park, Eun-Sung;Kim, Hyun-Jeong;Lee, Min-Ju;Lee, Ji-Yoon;Shin, Teo-Jeon;Seo, Kwang-Suk;Yum, Kwang-Won
    • Journal of The Korean Dental Society of Anesthesiology
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    • v.8 no.1
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    • pp.29-34
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    • 2008
  • 배경: 신경병증성 통증은 스테로이드, 아편유사제 등의 진통제에 잘 반응하지 않는다. 하지만 염증성 매개물질들이 신경병증성 통증의 발생에 관여한다는 보고가 있다. 특히 선택적 COX2 억제제인 celecoxib의 신경병증성 통증에 대한 효과에 관해서 상반된 연구결과가 존재한다. 본 연구는 신경병증성 통증 모델인 척추신경 결찰모델을 이용 기계적, 냉각 이질통 및 온도감각 과민현상의 발현에 celecoxib이 미치는 영향을 관찰하여 celecoxib의 항통각효과를 확인하고자 하였다. 방법: 30마리의 쥐를 이용 척추신경을 결찰하여 신경병증성 통증을 유도하였다 celecoxib (1, 10, 100, and 300 mg/kg)을 경구 투여하였고 총 30마리 중 12마리의 쥐에서 열, 기계적자극에 대해서 통각과민, 냉각자극에 의해 이질통이 발생하였다. 약물 투여 후 30, 60, 120, 180분 후 von Frey, 냉각자극검사, Hargreaves검사를 시행하여 쥐의 행동변화를 관찰하였다. 결과: 신경결찰 후 5일 후에 celecoxib의 용량에 관계없이 열, 기계적 자극에 의한 통각과민, 냉각 자극에 대한 이질통을 감소시키지 않았다(P > 0.05). 또한 celecoxib투여에 의한 장기간의 항 통각효과는 관찰되지 않았다(P > 0.05). 결론: celecoxib을 경구로 투여하였을 때 장기간 유지된 신경병증성 통증 흰쥐에서 약의 투여용량, 투여기간에 따른 항 통각작용은 관찰되지 않았다. 따라서 조직 손상후 발생된 장기간의 신경병증성 통증에 있어서 celecoxib은 효과가 없는 것으로 사료된다.

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Screening of Anticancer Potential of Celecoxib and its Derivatives (셀레콕시브 및 그 합성유도체들의 항암활성 스크리닝)

  • Park, Jeong-Ran;Kang, Jin-Hyoung;Kuh, Hyo-Jeong;Noh, Ji-Young;Ryu, Hyung-Chul;Park, Sang-Wook;Ko, Dong-Hyun;Cho, Il-Hwan;Lee, Joo-Y.;Hwang, Daniel-H.;Kim, In-Kyung
    • Journal of Pharmaceutical Investigation
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    • v.33 no.2
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    • pp.105-112
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    • 2003
  • Selective COX (cyclooxygenase)-2 inhibitors including celecoxib have been shown to induce apoptosis and cell cycle changes in various tumor cells. New inhibitors are recently being developed as chemomodulating agents. We evaluated celecoxib and screened 150 synthetic compounds for anti-proliferative activities in vitro. Effects of celecoxib on COX activity, cell growth, cell cycle distribution, and apoptosis induction were determined in A549 COX-2 overexpressing human non-small cell lung cancer (NSCLC) cells. The COX inhibition of celecoxib increased with concentration up to 82% at $1\;{\mu}M$ after 24 hr exposure. Forty ${\mu}M$ and $50\;{\mu}M$ of ce1ecoxib induced $G_1$ arrest, and TUNEL-positive apoptotic cells, respectively. Among 150 compounds, several compounds were selected for having greater COX-2 inhibitory activity and higher selectivity than celecoxib with growth inhibitory activity. Celecoxib showed concentration-dependent COX inhibitory activity, and ability to induce cell cycle arrest and apoptosis in human NSCLC cells in vitro. Among synthetic analogues screened, several compounds showed promising in vitro activity as COX-2 inhibitory anticancer agents, which warrant further evaluation in vitro and in vivo.

Solubility of celecoxib in N-methyl-2-pyrrolidone + water mixtures at various temperatures: Experimental data and thermodynamic analysis

  • Nozohouri, Sarah;Shayanfar, Ali;Cardenas, Zaira Johanna;Martinez, Fleming;Jouyban, Abolghasem
    • The Korean Journal of Chemical Engineering
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    • v.34 no.5
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    • pp.1435-1443
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    • 2017
  • Solubility is one of the most significant physicochemical properties of drugs, and improving the solubility of drugs is still a challenging subject in pharmaceutical sciences due to requirements of enhancing their bioavailability. Celecoxib, according to the biopharmaceutics classification system (BCS), is a class 2 drug, possessing low water solubility (<$5{\mu}g{\cdot}mL^{-1}$) and high permeability. Increasing the solubility of this group can lead to improved bioavailability, dose reduction and subsequently, increased efficiency and reduced side effects. In this study, celecoxib solubility was determined in binary mixtures of N-methyl-2-pyrrolidone (NMP)+water at 293.2, 298.2, 303.2, 308.2 and 313.2 K. The solubility of celecoxib is increased with the addition of NMP to the aqueous solutions and reaches a maximum value in neat NMP. In addition, increased temperature leads to enhanced solubility of celecoxib in a given solvent composition. The solubility data of celecoxib in NMP+water at different temperatures were correlated using different mathematical models including, the Jouyban-Acree model and a combination of the Jouyban-Acree and van't Hoff models. Thermodynamic parameters, Gibbs energy, enthalpy and entropy of dissolution processes were performed based on Gibbs and van't Hoff equations. Thermodynamic analysis allowed observing two main entropy or enthalpy-driven dissolution mechanisms, varying according to the composition of aqueous mixtures. Moreover, preferential solvation of celecoxib by water is observed in water-rich mixtures but preferential solvation by NMP was seen in mixtures with similar composition and also in NMP-rich mixtures.