The effect of nitric oxide on cyclooxygenase‐2 (COX‐2) overexpression in head and neck cancer cell lines

Park, Seok-Woo; Lee, Sang Goo; Song, Sang Hyun; Heo, Dae Seog; Park, Bum Jung; Lee, Dong Hoon; Kim, Kwang Hyun; Sung, Myung‐Whun

doi:10.1002/ijc.11498

Cited by 64 publications

(49 citation statements)

References 42 publications

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“…Recently, we showed that NO induces COX-2 expression and prostaglandin E 2 (PGE 2 ) production in head and neck cancer cells, and that this effect is blocked by iNOS inhibitors. Similar results have been shown in other cancer cells, including hepatocarcinoma, gastric cancer and cervical cancer (Park et al, 2003).…”

Section: Introductionsupporting

confidence: 89%

“…We previously reported that NO induces COX-2 expression in cancer cells (Park et al, 2003). Other groups have noted that while iNOS and COX-2 are barely detectable in resting inflammatory cells, their expression levels are transiently upregulated in response to signals such as growth factors and stress (Posadas et al, 2000;Surh et al, 2001).…”

Section: Discussionmentioning

confidence: 94%

“…We previously observed that NO induces COX-2 overexpression in various cancer cells (Park et al, 2003). To investigate whether the NO-induced responses identified in this study are seen in cancer cells other than SNU-1041, we tested the effect of NO on another head and neck cancer cell line (PCI-13) and two cell lines originating from other cancer types (SNU-668 and HeLa).…”

Section: The Effect Of No On Cox-2 Expression In Other Cancer Cellsmentioning

confidence: 92%

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Nitric oxide upregulates the cyclooxygenase-2 expression through the cAMP-response element in its promoter in several cancer cell lines

et al. 2005

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We previously showed that nitric oxide (NO) induces overexpression of cyclooxygenase-2 (COX-2) and production of prostaglandin E 2 in cancer cells. Here, we investigated the mechanisms by which NO induces COX-2 expression in cancer cells. We found that the cAMP-response element (CRE) is a critical factor in NOinduced COX-2 expression in all cells tested. We found that in cancer cells, three transcription factors (TFs) -cAMP response element-binding protein (CREB), activating transcription factor-2 (ATF-2) and c-jun, bound the CRE in the COX-2 promoter, and their activities were increased by addition of the NO donor, S-nitroso-Nacetyl-D,L-penicillamine (SNAP). NO-induced activation of soluble guanylate cyclase (sGC), p38 and c-Jun NH 2 -terminal kinase (JNK) upregulated the three TFs, leading to COX-2 overexpression. Addition of dibutyryl-cGMP (db-cGMP) induced COX-2 expression in a manner similar to SNAP; this induction was blocked by a p38 inhibitor (SB202190), but not by a JNK inhibitor (SP600125). NO-induced cGMP was found to activate CREB and ATF-2 in a p38, but not c-jun-dependent manner, while NO induced JNK in a cGMP-independent manner, leading to subsequent activation of c-jun and ATF-2. These results suggest that the low concentrations of endogenous NO present in cancer cell may induce the expression of many genes, including COX-2, which promotes the growth and survival of tumor cells.

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Section: Introductionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 94%

Section: The Effect Of No On Cox-2 Expression In Other Cancer Cellsmentioning

confidence: 92%

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Nitric oxide upregulates the cyclooxygenase-2 expression through the cAMP-response element in its promoter in several cancer cell lines

et al. 2005

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“…eNOS can regulate the expression of the proinflammatory molecules nuclear factor-κB (NF-κB) and COX-2 (19-21). Park et al (22) demonstrated that NO could increase COX-2 expression in many different cancer cell lines, including liver, cervical, and gastric cancer. They also reported that endogenous NO produced by NOS plays a key role in COX-2 expression and proposed that iNOS inhibitors could be used to regulate COX-2 expression in head and neck squamous cell carcinoma cells.…”

Section: Discussionmentioning

confidence: 99%

“…Inhibition of COX-2 activity by celecoxib reduces these effects, thereby suppressing angiogenesis and decreasing tumor growth (30). Park et al (22) reported that cross-talk exists between COX and NOS in head and neck cancer cell lines. There are inter- actions between COX and NOS pathways among host tissues, not only in tumor tissue (31)(32)(33).…”

Section: Discussionmentioning

confidence: 99%

Antitumor effects of inhibitors of nitric oxide synthase or cyclooxygenase-2 on human KB carcinoma cells overexpressing COX-2

Ohtsu

Takaoka²,

Segawa³

et al. 2010

Oncol Rep

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Abstract. Inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 are major inflammatory mediators. Nitric oxide (NO) produced by iNOS has been shown to have an important role in carcinogenesis. Recent studies have suggested that COX-2 expression also contributes to carcinogenesis, as well as tumor growth, invasion, and metastasis. COX-2 inhibitors such as celecoxib are widely recognized to have antitumor activity, but can cause adverse effects. We investigated possible relations between COX-2 and NO with the use of a human epidermoid carcinoma cell line, designated KB, in which overexpression of COX-2 protein was induced by gene transfer. We also assessed the possibility of using NOS inhibitor as an antitumor drug. We isolated a COX-2 transfected clone (KB/COX-2) and used a neomycin-transfected clone (KB/neo) as control. N G -nitro-Larginine-methyl ester (L-NAME) was used as a NOS inhibitor, dihydrochloride (1400W) as an iNOS inhibitor, and celecoxib as a selective COX-2 inhibitor. All agents inhibited the cell growth of both clones to similar extents in a dosedependent manner. Prostaglandin E 2 (PGE 2 ) production and COX-2 expression in KB/COX-2 were inhibited not only by celecoxib, but also by L-NAME and 1400W. The decreases in PGE 2 production and COX-2 expression were most prominent with celecoxib and L-NAME. In vivo, L-NAME and celecoxib significantly inhibited the proliferation of KB/COX-2-xenografted tumors. Tumor weight was reduced by L-NAME (60.6% decrease), 1400W (38.0% decrease), and celecoxib (74.5% decrease) as compared with the control after 21 days of treatment. Immunohistochemically, xenografted tumors expressed COX-2, iNOS, and eNOS. Such expression was suppressed by treatment with L-NAME and celecoxib. These results suggest that L-NAME and celecoxib significantly inhibit the proliferation of murine squamous cell carcinoma in vivo. L-NAME as well as celecoxib might thus be useful for the design and development of new antitumor drugs. IntroductionThe biosynthesis and release of nitric oxide (NO) and prostaglandins (PGs) share a number of similarities. Two major forms of nitric oxide synthase (NOS) and cyclooxygenase (COX) have been identified to date. NO is a multifunctional gaseous molecule synthesized from L-arginine by NOS. There are three isoforms of NOS: neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible isoform of NOS (iNOS). nNOS and eNOS are constitutively expressed and are also referred to as constitutive NOS (cNOS). In contrast, iNOS is transcriptionally regulated and induced by inflammatory cytokines, endotoxins, hypoxia, and oxidative stress (1,2). iNOS produces high, sustained concentrations of NO, whereas the other two isoforms produce low, transient concentrations of NO (3).Previous studies have shown positive correlations between iNOS and poor outcomes in patients with breast cancer and melanoma (4,5). These observations suggest that NO generated by iNOS has multiple physiologic and pathologic effects. It has been reported that eNOS can modulate cancer-related ...

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Head and Neck Cancer Recurrence and Mortality in Nonselective Cyclooxygenase Inhibitor Users

Gillespie¹,

Moody²,

Lee³

et al. 2007

Arch Otolaryngol Head Neck Surg

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To determine whether ongoing use of a cyclooxygenase (COX) inhibitor is associated with a reduction in mortality and disease recurrence after head and neck cancer treatment. Design: Retrospective case-control study. Patients: A total of 325 potential subjects with head and neck squamous cell carcinoma were identified using an electronic patient database. Main Outcome Measure: The rate of COX inhibitor use among patients who had died or whose disease had recurred (cases) was compared with the rate of use among survivors or those without recurrence (controls). The comparison was controlled for tumor site, tumor stage, treatment received, age, sex, race, smoking, and alcohol use. Results: The 325 patients were compared by logistic regressions, with recurrence rate and survival status as

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The effect of nitric oxide on cyclooxygenase‐2 (COX‐2) overexpression in head and neck cancer cell lines

Cited by 64 publications

References 42 publications

Nitric oxide upregulates the cyclooxygenase-2 expression through the cAMP-response element in its promoter in several cancer cell lines

Nitric oxide upregulates the cyclooxygenase-2 expression through the cAMP-response element in its promoter in several cancer cell lines

Antitumor effects of inhibitors of nitric oxide synthase or cyclooxygenase-2 on human KB carcinoma cells overexpressing COX-2

Head and Neck Cancer Recurrence and Mortality in Nonselective Cyclooxygenase Inhibitor Users

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