Topical inhibition of oral carcinoma cell with polymer delivered celecoxib

Wang, Zhi; Polavaram, Raju; Shapshay, Stanley M.

doi:10.1016/s0304-3835(03)00272-6

Cited by 21 publications

(23 citation statements)

References 16 publications

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“…As reported previously, celecoxib was anti-inflammatory and chemopreventive when given both systemically and topically in a UV-induced skin carcinogenesis model (43,44). Topical celecoxib in polymer film inhibited tumorigenesis of inoculated human oral cancer cells when applied at the site of inoculation (45). In this study, rather high concentrations of zileuton and celecoxib allowed local permeation into keratinized squamous epithelium of hamster oral mucosa.…”

Section: Discussionsupporting

confidence: 77%

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

Sood

Wang

et al. 2005

Clinical Cancer Research

119

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Purpose: Previous studies have suggested an important role of aberrant arachidonic acid metabolism, especially the cyclooxygenase (Cox) pathway, in oral carcinogenesis. However, it is unknown whether the 5-lipoxygenase (5-Lox) pathway contributes to oral carcinogenesis, and whether combination of inhibitors of both pathways may have synergistic or additive effects of chemoprevention.Experimental Design: 5-Lox expression was examined in 7,12-dimethylbenz[a]anthracene (DMBA) --induced hamster and human oral cancer tissues by immunohistochemistry, and Cox2 expression was investigated in hamster oral tissues using in situ hybridization. Zileuton (a specific 5-Lox inhibitor) and celecoxib (a specific Cox2 inhibitor), either alone or in combination, were investigated for their chemopreventive effects on the DMBA-induced hamster model at the post-initiation stage through topical application.Results: 5-Lox was overexpressed during oral carcinogenesis in hamsters and humans, as well as Cox2 in the hamster tissues. In a chemoprevention study using the postinitiation DMBA model, incidence of hamster oral squamous cell carcinoma was reduced from 76.9% (20 of 26) to 45.8% (11 of 24, P < 0.05) and 32.1% (9 of 28, P < 0.01) by 3% and 6% topical zileuton, respectively; and to 57.6% (15 of 26, P > 0.05) and 50% (12 of 24, P < 0.05) by 3% and 6% topical celecoxib, respectively. When used in combination, celecoxib and zileuton (3% of each) had an additive inhibitory effect on the incidence of squamous cell carcinoma (36%, 9 of 25, P < 0.01). Other pathologic variables and the levels of leukotriene B4 and prostaglandin E2 of the hamster tissues were reduced as well.Conclusions: The results clearly showed that both 5-Lox and Cox2 played important roles in oral carcinogenesis. Zileuton and celecoxib prevented oral carcinogenesis at the post-initiation stage through their inhibitory effects on arachidonic acid metabolism.

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Section: Discussionsupporting

confidence: 77%

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

Sood

Wang

et al. 2005

Clinical Cancer Research

119

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“…It shows high efficacy in the symptomatic treatment of osteoarthritis and rheumatoid arthritis in longterm therapy (1). Recently, research studies have indicated a potential role of Cx in chemoprevention of various cancers including oral cancer (2)(3)(4)(5)(6). Another study elected Cx as one of the drugs of choice to target COX-2 in oral epithelial cells by topical application in oral cancer chemoprevention using animal models due to its suitable physico-chemical and biochemical properties (7,8).…”

Section: Celecoxib (Cx) or 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-mentioning

confidence: 99%

“…However, toxic systemic side effects (increased risk of cardiovascular effects with continued use) limit its use for long periods of time, after oral administration (4,10). For this reason, in the treatment of localized inflammatory conditions or chemopreventive treatment by buccal administration of these drugs turns out to be a better strategy, reducing the risk of systemic toxicity while preserving the treatment efficacy.…”

Section: Celecoxib (Cx) or 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-mentioning

confidence: 99%

“…For this reason, in the treatment of localized inflammatory conditions or chemopreventive treatment by buccal administration of these drugs turns out to be a better strategy, reducing the risk of systemic toxicity while preserving the treatment efficacy. The exploration of Cx administration by other routes as buccal (3,4,8) or transdermal (11,12) has been explored to reformulate this drug for use in several inflammatory conditions. Nowadays, Cx is the only drug COX-2 inhibitor currently available in the market, the others being withdrawn from the market due to serious side effects.…”

Section: Celecoxib (Cx) or 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-mentioning

confidence: 99%

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In Vitro Characterization of Chitosan Gels for Buccal Delivery of Celecoxib: Influence of a Penetration Enhancer

et al. 2011

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Abstract. Celecoxib (Cx) shows high efficacy in the treatment of osteoarthritis and rheumatoid arthritis as a result of its high specificity for COX-2, without gastrolesivity or interference with platelet function at therapeutic concentrations. Besides of anti-inflammatory effects, Cx also has a potential role for oral cancer chemoprevention. For these conditions, oral administration in long-term treatment is a concern due to its systemic side effects. However, local application at the site of injury (e.g., buccal inflammation conditions or chemoprevention of oral cancer) is a promising way to reduce its toxicity. In this study, the in vitro characterization of mucoadhesive chitosan (CHT) gels associated to Azone® was assessed to explore the potential buccal mucosal administration of Cx in this tissue. Rheological properties of gels were analyzed by a rheometer with cone-plate geometry. In vitro Cx release and permeability studies used artificial membranes and pig cheek mucosa, respectively. Mucoadhesion were measured with a universal test machine. CHT gels (3.0%) containing 2.0% or 3.0% Az showed more appropriate characteristics compared to the others: pH values, rheology, higher amount of Cx retained in the mucosa, and minimal permeation through mucosa, besides the highest mucoadhesion values, ideal for buccal application. Moreover, the flux (J) and amounts of drug released decreased with increased CHT and Az concentrations. CHT gels (3.0%) associated with 2.0% or 3.0% Az may be considered potential delivery systems for buccal administration of Cx.

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“…As preventive agents, they must possess minimal toxicity for long-term therapy. Novel methods of administration have been evaluated to maximize exposure while minimizing toxicity, with topical therapy being an effective method of administration in animal models (39). These considerations prompted Mulshine et al (40) to conduct a randomized, doubleblind, placebo-controlled, trial of the NSAID ketorolac as an oral rinse in oropharyngeal leukoplakia patients.…”

Section: Limitations Of Nsaids For Chemoprevention In the Oral Mucosamentioning

confidence: 99%

NSAIDs for the Chemoprevention of Oral Cancer: Promise or Pessimism?

Goodin¹,

Shiff²

2004

Clinical Cancer Research

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Topical inhibition of oral carcinoma cell with polymer delivered celecoxib

Cited by 21 publications

References 16 publications

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

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

In Vitro Characterization of Chitosan Gels for Buccal Delivery of Celecoxib: Influence of a Penetration Enhancer

NSAIDs for the Chemoprevention of Oral Cancer: Promise or Pessimism?

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