• Title, Summary, Keyword: COX-2

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Evaluation of Cytotoxicity Effects of Chalcone Epoxide Analogues as a Selective COX-II Inhibitor in the Human Liver Carcinoma Cell Line

  • Makhdoumi, Pouran;Zarghi, Afshin;Daraei, Bahram;Karimi, Gholamreza
    • Journal of Pharmacopuncture
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    • v.20 no.3
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    • pp.207-212
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    • 2017
  • Objectives: Study of the mechanisms involved in cancer progression suggests that cyclooxygenase enzymes play an important role in the induction of inflammation, tumor formation, and metastasis of cancer cells. Thus, cyclooxygenase enzymes could be considered for cancer chemotherapy. Among these enzymes, cyclooxygenase 2 (COX-2) is associated with liver carcinogenesis. Various COX-2 inhibitors cause growth inhibition of human hepatocellular carcinoma cells, but many of them act in the COX-2 independent mechanism. Thus, the introduction of selective COX-2 inhibitors is necessary to achieve a clear result. The present study was aimed to determine the growth-inhibitory effects of new analogues of chalcone epoxide as selective COX-2 inhibitors on the human hepatocellular carcinoma (HepG2) cell line. Methods: Estimation of both cell growth and the amount of prostaglandin E2 (PGE2) production were used to study the effect of selective COX-2 inhibitors on the hepatocellular carcinoma cell. Cell growth determination has done by MTT assay in 24 h, 48 h and 72 h, and PGE2 production has estimated by using ELYSA kit in 48 h and 72 h. Results: The results showed growth inhibition of the HepG2 cell line in a concentration and time-dependent manner, as well as a reduction in the formation of PGE2 as a product of COX-2 activity. Among the compounds those analogues with methoxy and hydrogen group showed more inhibitory effect than others. Conclusion: The current in-vitro study indicates that the observed significant growth-inhibitory effect of chalcone-epoxide analogues on the HepG2 cell line may involve COX-dependent mechanisms and the PGE2 pathway parallel to the effect of celecoxib. It can be said that these analogues might be efficient compounds in chemotherapy of COX-2 dependent carcinoma specially preventing and treatment of hepatocellular carcinomas.

A New Class of Selective COX-2 Inhibitor: Luotonin A Homologues and their Aza-analogues (새로운 계열의 선택적 COX-2 저해제: Luotonin A 동족체 및 그 질소 유도체)

  • Kim, Dong-Hyeon;Liang, Jing-Liu;Oh, Joon-Seok;Jahng, Yurng-Dong;Kim, Jin-Cheul;Hong, Tae-Gyun;Hwang, Nam-Kyung;Chung, Hwan-Ki;Kim, Yun-Kyung;Chang, Hyeun-Wook
    • YAKHAK HOEJI
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    • v.51 no.5
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    • pp.313-317
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    • 2007
  • A series of luotonin A homologues and their aza-analogues were prepared and evaluated their inhibitory activities on COX-1 and 2 as well as their selectivities on COX-2. The aza-analogue of dimethylene-bridged homologue of luotonin A, 3,3'-dimethylene-2-(1',8'-naphthyrid-2'-yl)-4(3H)-quinazolinone (2b), exhibited strongest inhibitory activity against COX-1 and COX-2 dependent phase of prostaglandin $D_2$ generation in mouse bone marrow-derived mast cells in a concentration-dependent manner with an $IC_{50}$ of 39.3 and $1.89{\mu}M$, respectively. Selectivity of 2b on COX-2 over COX-1 was 21 which implied 2b can be a potential lead for the development of selective COX-2 inhibitor.

Expression of Cox-2 and Bcl-2 in Paget's Disease of the Breast

  • Alikanoglu, Arsenal Sezgin;Yildirim, Mustafa;Suren, Dinc;Tutus, Birsel;Kaya, Vildan;Topal, Cumhur Selcuk;Keser, Sevinc;Karadayi, Ayse Nimet;Kapucuoglu, Fatma Nilgun;Ayva, Sebnem;Gunduz, Seyda
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.3
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    • pp.1041-1045
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    • 2015
  • Background: Paget's disease (PD) is a rare form of intraepithelial adenocarcinoma that involves breast and extramammarian tissues. It is often associated with ductal carcinoma in situ and/or invasive ductal cancer. Molecular pathways that play a role in development of Paget's disease are stil unclear. Expression patterns of Cox-2 and bcl-2 were therefore assessed. Materials and Methods: Patients with a histopathological diagnosis of Paget's disease were included in this study. Patient files were analysed retrospectively. Results: Invasive cancer was diagnosed in 35 (76.1%) of the patients, 7 (15.2%) had ductal carcinoma in situ and 4 (8.7%) patients had no associated neoplasm. Twenty four (52.2%) patients showed COX-2 expression in Paget cells whereas no expression was seen in 22 (47.8%) patients. No relation was found between COX-2 expression and the lesion underlying Paget's disease (p=0.518). Bcl-2 expression in Paget cells was found positive in 12 (26.1%) and negative in 27 (58,7%) cases. There was no relation between Bcl-2 expression and the lesion accompanying Paget's disease (p=0.412). No relation was observed between COX-2 expression and Bcl-2 expression (p=0.389). Conclusions: In breast cancer, COX-2 expression is associated with poor prognostic factors. As COX-2 expression increases the tendency to metastasize also increases. In our study we found a significantly high COX-2 expression in Paget's disease of the breast. We suggest that COX-2 expression and inflammatory processes may play a role in pathogenesis of the Paget's disease of the breast.

INTERACTIONS BETWEEN COX-2 AND NITRIC OXIDE SYNTHASE OF ESTROGEN AND ISOFLAVONES IN VIVO

  • Shin, Jane-In;Park, Ock-Jin
    • Proceedings of the Korean Society of Toxicology Conference
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    • pp.88-88
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    • 2002
  • Cyclooxygenase(COX) metabolizes arachidonic acid to prostaglandins and thromboxanes. It has been reported that there is 'cross-talk' between COX-2 and nitric oxide synthase(NOS). Stimulation of eNOS of estrogen fed animal heart was not accompanied by the increase in COX-2 expression.(omitted)

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Effects of Astaxanthin on the Production of NO and the Expression of COX-2 and iNOS in LPS-Stimulated BV2 Microglial Cells

  • Choi, Seok-Keun;Park, Young-Sam;Choi, Dong-Kug;Chang, Hyo-Ihl
    • Journal of Microbiology and Biotechnology
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    • v.18 no.12
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    • pp.1990-1996
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    • 2008
  • Astaxanthin has shown antioxidant, antitumor, and anti-inflammatory activities; however, its molecular action and mechanism in the nervous system have yet to be elucidated. We examined the in vitro effects of astaxanthin on the production of nitric oxide (NO), as well as the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Astaxanthin inhibited the expression or formation of nitric oxide (NO), iNOS and COX-2 in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. Astaxanthin also suppressed the protein levels of iNOS and COX-2 in LPS-stimulated BV2 microglial cells. These results suggest that astaxanthin, probably due to its antioxidant activity, inhibits the production of inflammatory mediators by blocking iNOS and COX-2 activation or by the suppression of iNOS and COX-2 degradation.

Cyclooxygenase-2 Expression in Benign and Malignant Chondroid Tumors (양성 및 악성 연골 종양의 Cyclooxygenase-2 발현)

  • Park, Hye-Rim;Min, Kwang-Seon;Park, Yong-Koo
    • The Journal of the Korean bone and joint tumor society
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    • v.13 no.2
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    • pp.105-112
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    • 2007
  • Purpose: Recent studies have shown increased levels of cyclooxygenase-2 (COX-2) in various human malignancies to include various bone and soft tissue tumors. However, little is known with regard to COX-2 expression patterns in chondroid tumors. Materials and Methods: Immunohistochemistry assays were performed for COX-2 in enchondromas (n=10), chondroblastomas (n=11), chondromyxoid fibromas (n=5), conventional chondrosarcomas (n=17), clear cell chondrosarcomas (n=7), and mesenchymal chondrosarcomas (n=6). Results: Among the benign chondroid tumors, chondroblastomas revealed characteristic strong positivity in 6 of 11 cases(54.5%). All enchondromas and chondromyxoid fibromas were negative except in one case. In conventional chondrosarcomas, three cases(17.6%) were strongly reactive with COX-2 and all positive cases represented grade III chondrosarcomas. Clear cell chondrosarcomas were found to be focally positive in two cases(28.5%), while all mesenchymal chondrosarcomas were negative. Conclusions: These findings suggest that COX-2 overexpression in conventional chondrosarcoma may represent an advanced histologic grade. Interestingly, expression of COX-2 in chondroblastomas could be an important factor for inducing peritumoral inflammatory changes in these specific tumors.

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Prognostication by Cluster Analysis of COX-2, MMP-9 and P53 Expression and by Clinico-pathologic Correlation Analysis in Non-small Cell Lung Cancer (비소세포폐암에서 COX-2,MMP-9와 돌연변이형 p53 의 발현이 생존에 대한 예후 분석)

  • Shin, Jong Wook;Choi, Jae Ho;Park, In Won;Yoo, Jae Hyung
    • Tuberculosis and Respiratory Diseases
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    • v.63 no.1
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    • pp.31-41
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    • 2007
  • Background: In pathogenesis and prognosis of lung cancer, significance of enormous types of genetic expression were very compounding and undetermined. We performed this study to search association between clinical characteristics and expression of COX-2, MMP-9 and p53 in non-small cell lung cancer. Methods: Ninety-one patients with adenocarcinoma or squamous cell carcinoma were enrolled. We had searched clinical data retrospectively and performed immunohistochemical staining for COX-2, MMP-9 and p53. We had analyzed significance of these three genes in clinical features and prognosis for survival. Results: 1) In squamous cell carcinoma, male was predominant and was significantly correlated with smoking. 2) Major prognostic determinants for overall survival were curative resection. 3) Expression of COX-2 was more frequent in adenocarcinoma than in squamous cell carcinoma. 4) Negative staining of COX-2, MMP-9 and p53 was more frequent in squamous cell carcinoma than adenocarcinoma. 5) Survival duration was longer in the group with positive expression of p53 and negative for COX-2 and MMP-9 (median duration of survival = 165.6 weeks) than groups with the other expressional patterns. 6) Significant correlation was found between expression of MMP-9 and COX-2. In squamous cell carcinoma, expression of MMP-9, COX-2 and mutant p53 were mutually correlated. 7) COX-2 expression was significant prognostic factor for survival in resected cancer group. In unresected inoperable non-small cell lung cancer group, MMP-9 was statistically significant prognostic factor for overall survival. Conclusion: COX-2 and MMP-9 might have some roles for progression or prognosis in some selected patients with non-small cell lung cancer. COX-2 and MMP-9 may have some roles for disease progression or prognosis in selected patients with NSCLC.

Autocrine prostaglandin E2 signaling promotes promonocytic leukemia cell survival via COX-2 expression and MAPK pathway

  • Shehzad, Adeeb;Lee, Jaetae;Lee, Young Sup
    • BMB Reports
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    • v.48 no.2
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    • pp.109-114
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    • 2015
  • The COX-2/$PGE_2$ pathway has been implicated in the occurrence and progression of cancer. The underlying mechanisms facilitating the production of COX-2 and its mediator, $PGE_2$, in cancer survival remain unknown. Herein, we investigated $PGE_2$-induced COX-2 expression and signaling in HL-60 cells following menadione treatment. Treatment with $PGE_2$ activated anti-apoptotic proteins such as Bcl-2 and Bcl-xL while reducing pro-apoptotic proteins, thereby enhancing cell survival. $PGE_2$ not only induced COX-2 expression, but also prevented casapse-3, PARP, and lamin B cleavage. Silencing and inhibition of COX-2 with siRNA transfection or treatment with indomethacin led to a pronounced reduction of the extracellular levels of $PGE_2$, and restored the menadione- induced cell death. In addition, pretreatment of cells with the MEK inhibitor PD98059 and the PKA inhibitor H89 abrogated the $PGE_2$-induced expression of COX-2, suggesting involvement of the MAPK and PKA pathways. These results demonstrate that $PGE_2$ signaling acts in an autocrine manner, and specific inhibition of $PGE_2$ will provide a novel approach for the treatment of leukemia.

New screening method for anti-inflammatory agent (Cyclooxygenase 억제제 검색을 통한 항염증제 개발 연구)

  • Lee, Su-Hwan;Jeong, Seong-Won;Lee, U-Yeong
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.20 no.1
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    • pp.25-36
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    • 1994
  • It is weal known that bacterial lipopolysaccharide (LPS) stimulates prostaglandin synthesis in various experimental system via enhancing the expression of cylooxygenase-2 (COX-2). This study was designed to characterize U)5-induced prostaglandin synthesis in mouse peritoneal macrophages LPS-stimulated prostaglandin synthesis in macrophages with short term exposure was not so much prominent, but there was a burst in prostaglandin synthesis 8 hours after the LPS treatment and this u·as accompanied with the increase of cyclooxygenase activity, Dexamethasone markedly inhibited prostaglandin synthesis in this system. Metabolic label ins data supported above observations and thus, it could be concluded that LPS induces the do novo synthesis of COX-2 by which it stimulates the prostaglandin synthesis in mouse peritoneal macrophages, These data suggested that this experimental model system could be used for the screening procedure of COX-2 selective inhibitors. Ketoprofen, a non steroidal anti inflammatory agent, appeared to inhibit COX-1 relatively more selectively than COX-2.

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Cyclooxygenase-2 as a Molecular Target for Cancer Chemopreventive Agents

  • Surh, Young-Joon
    • Toxicological Research
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    • v.17
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    • pp.89-96
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    • 2001
  • Recently, considerable attention has been focused on the role of cyclooxygenase-2 (COX-2) in the carcinogenesis as well as in inflammation. Improperly overexpressed COX-2 has been observed in many types of human cancers and transformed cells in culture. Thus, it is conceivable that targeted inhibition of abnormally or improperly up-regulated COX-2 provides one of the most effective and promising strategies for cancer prevention. A ubiquitous eukaryotic transcription factor, NF-kB is considered to be involved in regulation of COX-2 expression. Furthermore, extracellular-regulated protein kinase and p38 mitogen-activated protein (MAP) kinase appear to be key elements of the intracellular signaling cascades involved in NF-kB activation in response to a wide array of external stimuli. Certain chemopreventive phytochemicals suppress activation of NF-kB by blocking one or more of the MAP kinases, which may contribute to their inhibitory effects on COX-2 induction. One of the plausible mechanisms by which chemopreventive phytochemicals inhibit NF-kB activation involves suppression of degradation of the inhibitory unit I kB, which hampers subsequent translocation of p65, the functionally active subunit of NF-kB.

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