Overexpression of 5-Lipoxygenase and Cyclooxygenase 2 in Hamster and Human Oral Cancer and Chemopreventive Effects of Zileuton and Celecoxib

Li, Ning; Sood, Sandeep; Wang, Su; Fang, Mingzhu; Wang, Peng; Sun, Zheng; Yang, Chung S.; Chen, Xiaoxin

doi:10.1158/1078-0432.ccr-04-1684

Cited by 119 publications

(84 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…41 More recently, overexpression of LTA 4 H and 5-LOX protein was demonstrated in rat and human esophageal adenocarcinoma 42,43 and hamster and human oral cancer. 44,45 Our data showing overexpression of LTA 4 H protein in lingual lesions/ SCC from ZD rats, as well as in forestomach lesions/SCC from ZD:COX2/2 mice, are consistent with the idea that 5-LOX/ LTA 4 H pathway is of importance in oral carcinogenesis. 45 It is now recognized that NF-jB provides a link between inflammation/immunity and cancer development/progression; and the IjB kinase/NF-jB activation pathway is a target for cancer prevention.…”

Section: Discussionsupporting

confidence: 85%

Prevention of upper aerodigestive tract cancer in zinc‐deficient rodents: Inefficacy of genetic or pharmacological disruption of COX‐2

Fong¹,

Jiang²,

Riley³

et al. 2007

Intl Journal of Cancer

View full text Add to dashboard Cite

Zinc deficiency in humans is associated with an increased risk of upper aerodigestive tract (UADT) cancer. In rodents, zinc deficiency predisposes to carcinogenesis by causing proliferation and alterations in gene expression. We examined whether in zinc-deficient rodents, targeted disruption of the cyclooxygenase (COX)-2 pathway by the COX-2 selective inhibitor celecoxib or by genetic deletion prevent UADT carcinogenesis. Tongue cancer prevention studies were conducted in zinc-deficient rats previously exposed to a tongue carcinogen by celecoxib treatment with or without zinc replenishment, or by zinc replenishment alone. The ability of genetic COX-2 deletion to protect against chemically-induced forestomach tumorigenesis was examined in mice on zinc-deficient versus zinc-sufficient diet. The expression of 3 predictive biomarkers COX-2, nuclear factor (NF)-j B p65 and leukotriene A 4 hydrolase (LTA 4 H) was examined by immunohistochemistry. In zinc-deficient rats, celecoxib without zinc replenishment reduced lingual tumor multiplicity but not progression to malignancy. Celecoxib with zinc replenishment or zinc replenishment alone significantly lowered lingual squamous cell carcinoma incidence, as well as tumor multiplicity. Celecoxib alone reduced overexpression of the 3 biomarkers in tumors slightly, compared with intervention with zinc replenishment. Instead of being protected, zinc-deficient COX-2 null mice developed significantly greater tumor multiplicity and forestomach carcinoma incidence than wild-type controls. Additionally, zinc-deficient COX-22/2 forestomachs displayed strong LTA 4 H immunostaining, indicating activation of an alternative pathway under zinc deficiency when the COX-2 pathway is blocked. Thus, targeting only the COX-2 pathway in zinc-deficient animals did not prevent UADT carcinogenesis. Our data suggest zinc supplementation should be more thoroughly explored in human prevention clinical trials for UADT cancer. ' 2007 Wiley-Liss, Inc.Key words: zinc deficiency; upper aerodigestive tract cancer; chemoprevention; COX-2; COX-2 null mice Upper aerodigestive tract (UADT) cancer, including esophageal and oral cancer, is an important cause of morbidity and mortality worldwide. 1 With a 5-year survival of 10%, esophageal cancers are deadly. The prognosis of oral cancer, the major site being the tongue, is equally dismal, with an increasing incidence worldwide, particularly in young adults. 2 Patients with oral cancer have a high mortality rate, because of field cancerization effects that result in second primary tumors, particularly in the esophagus. 3,4 Thus, new chemopreventive and therapeutic approaches are much needed to prevent and treat these deadly cancers.While chronic alcohol consumption and tobacco use are the major risk factors for UADT cancer, epidemiologic and clinical studies have implicated dietary zinc deficiency (ZD) in the etiology of esophageal squamous cell carcinoma (SCC) and head and neck SCC. [5][6][7][8][9] In 2005, Abnet et al. 10 provided the strongest evidence of an a...

show abstract

Section: Discussionsupporting

confidence: 85%

Prevention of upper aerodigestive tract cancer in zinc‐deficient rodents: Inefficacy of genetic or pharmacological disruption of COX‐2

Fong¹,

Jiang²,

Riley³

et al. 2007

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…Overexpression of COX2 has been found in human oral cancer and DMBA induced hamster cheek pouch tumor (29,30). In the present study, we found that in tumor samples of Hras128 rats treatment of 4NQO caused a marked increase in the levels of mRNA expression of cyclin D1 and COX2, when compared to the adjacent normal mucosa (Fig.…”

Section: Discussionsupporting

confidence: 65%

Enhancement of tongue carcinogenesis in Hras128 transgenic rats treated with 4-nitroquinoline 1-oxide

Naoi

Sunagawa²,

Yoshida³

et al. 2009

Oncol Rep

View full text Add to dashboard Cite

Abstract. Transgenic rats carrying human c-Ha-ras protooncogene (Hras128 rats) have been shown to be highly susceptible to induction of tumors. We have found an early induction of tongue tumors in Hras128 rats treated with 4-nitroquinoline 1-oxide (4NQO). 4NQO was administered to the Hras128 and wild-type Sprague-Dawley (SD) rats for 4 and 8 weeks, respectively. The experiment was terminated at 14 (Hras128 rats) and 28 (SD rats) weeks. Either during or after treatment with 4NQO, dysplastic hyperplasia, papilloma and squamous cell carcinoma were found on the tongue of both Hras128 and wild-type rats, with a higher incidence and multiplicity in Hras128 rats. Treatment of the Hras128 rats with 4NQO significantly increased cell proliferation in the tumor compared to the control rats. In the tongue tumors of the Hras128 rats, there was a significant increase in the mRNA expression levels of cyclin D1 and COX2. To examine whether this experimental system is useful for screening of the candidate agents for cancer preventive effect, nimesulide, a selective COX2 inhibitor, was tested in the present model. Nimesulide significantly decreased total multiplicity of tongue lesions compared to the control rats. Treatment of Hras128 rats with nimesulide caused a significant decrease in the levels of mRNA expression of cyclin D1 and COX2 in the tumor. Therefore, the current 4NQO-induced Hras128 rat tongue carcinogenesis model provides a simple and rapid system for investigating carcinogenesis process and evaluating the effect of possible cancer preventive agents for human tongue cancer.

show abstract

“…Topical treatment thrice every week for 18 weeks with 3% and 6% zileuton (a specific 5-lipoxygenase inhibitor) reduced the incidence of SCC from 76.9% to 45.8% (P < 0.05) and 32.1% (P < 0.0001) respectively, and treatment with celecoxib 6% to 50% (P < 0.05). The combination of celecoxib 3% with zileuton 3% reduced the SCC incidence to 36% (P < 0.05), suggesting an additive effect of celecoxib and zileuton in the HOCM (37).…”

Section: Discussionmentioning

confidence: 93%

“…In another study (37), hamsters were treated with 0.5% DMBA thrice every week for 6 weeks. Topical treatment thrice every week for 18 weeks with 3% and 6% zileuton (a specific 5-lipoxygenase inhibitor) reduced the incidence of SCC from 76.9% to 45.8% (P < 0.05) and 32.1% (P < 0.0001) respectively, and treatment with celecoxib 6% to 50% (P < 0.05).…”

Section: Discussionmentioning

confidence: 99%

In VivoAntineoplastic Effects of the NSAID Sulindac in an Oral Carcinogenesis Model

Katoumas

Nikitakis

Perrea

et al. 2015

Cancer Prevention Research

View full text Add to dashboard Cite

The antineoplastic properties of the NSAID sulindac have long been studied. The purpose of this study was to explore sulindac's in vivo effects on oral squamous cell carcinoma (SCC) oncogenesis using the hamster cheek pouch oral carcinogenesis model (HOCM). Thirty Syrian golden hamsters were divided into three experimental and two control groups (n ¼ 6 each). The animals' right buccal pouches were treated with carcinogen for 9 weeks in one experimental and one control group and for 14 weeks in all other three groups. The animals of two experimental groups received sulindac from the 1st week and those of the third experimental group from the 10th week. After the end of carcinogenesis, treated buccal pouches were removed and examined. In animals treated with carcinogen for 14 weeks, development of oral SCC and tumor volume were significantly lower in animals that received sulindac from the first week of the experiment. Oral SCC developing in animals that received sulindac were more frequently well differentiated compared with the control group. In animals treated with carcinogen for 9 weeks, the animals that received sulindac developed lower grade of epithelial dysplasia. Proliferation index Ki-67 and positivity for the antiapoptotic molecule survivin were lower in the animals that received sulindac. Treatment with sulindac appears to delays the progression of oral premalignant lesions to oral SCC in the HOCM, also resulting in smaller and better differentiated tumors. These in vivo antineoplastic effects may be related to sulindac's ability to decrease cell proliferation and to prevent survivin expression.

show abstract

Overexpression of 5-Lipoxygenase and Cyclooxygenase 2 in Hamster and Human Oral Cancer and Chemopreventive Effects of Zileuton and Celecoxib

Cited by 119 publications

References 40 publications

Prevention of upper aerodigestive tract cancer in zinc‐deficient rodents: Inefficacy of genetic or pharmacological disruption of COX‐2

Prevention of upper aerodigestive tract cancer in zinc‐deficient rodents: Inefficacy of genetic or pharmacological disruption of COX‐2

Enhancement of tongue carcinogenesis in Hras128 transgenic rats treated with 4-nitroquinoline 1-oxide

In VivoAntineoplastic Effects of the NSAID Sulindac in an Oral Carcinogenesis Model

Contact Info

Product

Resources

About