Anti-inflammatory, anti-proliferative and antioxidant profiles of selective cyclooxygenase-2 inhibition as chemoprevention for rat bladder carcinogenesis

Parada, B.; Sereno, José; Reis, Flávio; Teixeira-Lemos, Edite; Garrido, Patrícia; Pinto, Ângela Filipa Fonseca; Cunha, Maria Fernanda; Pinto, Rui; Mota, A.; Figueiredo, Arnaldo; Teixeira, Frederico

doi:10.4161/cbt.8.17.9199

Cited by 19 publications

(19 citation statements)

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“…Thus, an early treatment targeting these pathways could hypothetically prevent bladder cancer development and growth. Previous reports have demonstrated beneficial effects of preventive strategies [13], including our own studies using anti-inflammatory and anti-proliferative agents [14,15]. …”

Section: Introductionmentioning

confidence: 95%

“…Beyond their anti-dyslipidaemic properties, statins exhibit many other biological activities, known as pleiotropic effects [19]. Statins have been shown anti-inflammatory, anti-proliferative, antioxidant and anti-apoptotic properties [20–22], which could have an important role in bladder tumor prevention [23], particularly when considering that these pathways are up-regulated in this type of cancer [14,15]. The chemopreventive efficacy of statins was already demonstrated in other types of tumors, including in the pancreatic and the prostate cancers, resulting in retardation of tumor growth and/or inhibition of the metastatic process [24,25].…”

Section: Introductionmentioning

confidence: 99%

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Chemopreventive Efficacy of Atorvastatin against Nitrosamine-Induced Rat Bladder Cancer: Antioxidant, Anti-Proliferative and Anti-Inflammatory Properties

Parada

Reis

Pinto

et al. 2012

IJMS

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To investigate the anti-carcinogenic effects of Atorvastatin (Atorva) on a rat bladder carcinogenesis model with N-butyl-N-(4-hydroxibutil)nitrosamine (BBN), four male Wistar rat groups were studied: (1) Control: vehicle; (2) Atorva: 3 mg/kg bw/day; (3) Carcinogen: BBN (0.05%); (4) Preventive Atorva: 3 mg/kg bw/day Atorva + BBN. A two phase protocol was used, in which the drug and the carcinogen were given between week 1 and 8 and tumor development or chemoprevention were expressed between week 9 and 20, when the bladders were collected for macroscopic, histological and immunohistochemical (p53, ki67, CD31) evaluation. Serum was assessed for markers of inflammation, proliferation and redox status. The incidence of bladder carcinoma was: control 0/8 (0%); Atorva 0/8 (0%); BBN 13/20 (65%) and Atorva + BBN 1/8 (12.5%). The number and volume of tumors were significantly lower in the Atorva + BBN group, with a marked reduction in hyperplasia, dysplasia and carcinoma in situ lesions. An anti-proliferative, anti-inflammatory and antioxidant profile was also observed in the preventive Atorva group. p53 and ki67 immunostaining were significantly increased in the BBN-treated rats, which was prevented in the Atorva + BBN group. No differences were found for CD31 expression. In conclusion, Atorvastatin had a clear inhibitory effect on bladder cancer development, probably due to its antioxidant, anti-proliferative and anti-inflammatory properties.

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Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Chemopreventive Efficacy of Atorvastatin against Nitrosamine-Induced Rat Bladder Cancer: Antioxidant, Anti-Proliferative and Anti-Inflammatory Properties

Parada

Reis

Pinto

et al. 2012

IJMS

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“…Therefore, an effective strategy for preventing the progression of bladder cancer is clearly needed. Cyclooxygenase-2 (Cox-2) is overexpressed in high-grade invasive TCC, and the anti-tumour effect of Cox-2 inhibitors in invasive TCC of urinary bladder has been suggested in both pre-clinical and clinical studies (Okamoto et al , 2008; Parada et al , 2009; Qin et al , 2009; Dhawan et al , 2010). However, the mechanism of action for the anti-tumour effects of Cox-2 inhibitors is unclear.…”

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confidence: 99%

In vitro and in vivo inhibitory effect of three Cox-2 inhibitors and epithelial-to-mesenchymal transition in human bladder cancer cell lines

et al. 2011

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Background:Although the anti-tumour effect of cyclooxygenase-2 (Cox-2) inhibitors in invasive bladder cancer has been confirmed, its mechanisms of action are unclear. Recently, the concept of an epithelial-to-mesenchymal transition (EMT) promoting carcinoma progression has been suggested, and a key feature of the EMT is the downregulation of E-cadherin. In this study, we investigated the effect of Cox-2 inhibitors on reversal EMT and tumour growth inhibition in bladder cancer cells.Methods:We used three Cox-2 inhibitors, etodolac, celecoxib and NS-398 and three human bladder cancer cell lines, T24, 5637 and KK47, in this study. T24 xenograft tumour mouse model was used in the in vivo study.Results:Within the clinical drug concentrations, only etodolac showed the in vitro growth inhibition in T24 not in the other cell lines. Etodolac reduced SNAIL mRNA and vimentin cell surface expression, and induced E-cadherin mRNA and E-cadherin cell surface expression, in T24. Etodolac also most strongly inhibited the cell migration of T24 in vitro and showed the highest tumour growth inhibition in T24 tumour in vivo.Conclusion:Etodolac at clinical doses exhibited induced in vitro and in vivo anti-tumour effects and reversal effect of EMT in T24. These results suggest that etodolac is a good candidate for an anti-tumour or chemopreventive reagent for high-grade bladder cancer.

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“…The main purpose was the assessment of whether the COX-2 inhibitor celecoxib is effective as preventive or curative therapy for bladder carcinogenesis in an animal model previously described in the literature using 0.05% of BBN as the carcinogen inductor [22]. …”

Section: Discussionmentioning

confidence: 99%

“…Bladder cancer, induced in rats with the carcinogen N -butyl- N -(4-hydroxybutyl) nitrosamine (BBN), has been used as a model for study pathophysiology and therapeutics of this cancer [22], particularly due to the histological similarities with the human transitional cell carcinoma [23, 24]. Previous studies have demonstrated a positive response to some prevention strategies [25, 26], but the curative efficacy of new and promising pharmacological options, such as the celecoxib, remains to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Preventive but Not Curative Efficacy of Celecoxib on Bladder Carcinogenesis in a Rat Model

Parada

Reis

Cunha

et al. 2010

Mediators of Inflammation

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To evaluate the effect of a cyclooxygenase 2 inhibitor, celecoxib (CEL), on bladder cancer inhibition in a rat model, when used as preventive versus as curative treatment. The study comprised 52 male Wistar rats, divided in 5 groups, during a 20-week protocol: control: vehicle, carcinogen: 0.05% of N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN), CEL: 10 mg/kg/day of the selective COX-2 inhibitor Celebrex, preventive CEL (CEL+BBN-P), and curative CEL (BBN+CEL-C) groups. Although tumor growth was markedly inhibited by the preventive application of CEL, it was even aggravated by the curative treatment. The incidence of gross bladder carcinoma was: control 0/8(0%), BBN 13/20(65%), CEL 0/8(0%), CEL+BBN-P 1/8(12.5%), and BBN+CEL-C 6/8(75%). The number and volume of carcinomas were significantly lower in the CEL+BBN-P versus BBN, accompanied by an ample reduction in hyperplasia, dysplasia, and papillary tumors as well as COX-2 immunostaining. In spite of the reduction of tumor volumes in the curative BBN+CEL-C group, tumor malignancy was augmented. An anti-inflammatory and antioxidant profile was encountered only in the group under preventive treatment. In conclusion, preventive, but not curative, celecoxib treatment promoted a striking inhibitory effect on bladder cancer development, reinforcing the potential role of chemopreventive strategies based on cyclooxygenase 2 inhibition.

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Anti-inflammatory, anti-proliferative and antioxidant profiles of selective cyclooxygenase-2 inhibition as chemoprevention for rat bladder carcinogenesis

Cited by 19 publications

References 37 publications

Chemopreventive Efficacy of Atorvastatin against Nitrosamine-Induced Rat Bladder Cancer: Antioxidant, Anti-Proliferative and Anti-Inflammatory Properties

Chemopreventive Efficacy of Atorvastatin against Nitrosamine-Induced Rat Bladder Cancer: Antioxidant, Anti-Proliferative and Anti-Inflammatory Properties

In vitro and in vivo inhibitory effect of three Cox-2 inhibitors and epithelial-to-mesenchymal transition in human bladder cancer cell lines

Preventive but Not Curative Efficacy of Celecoxib on Bladder Carcinogenesis in a Rat Model

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