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• Fernandes, JC.
• Sereno, J
• Garrido, P
• Parada, B
• Cunha, MF. X.
• Reis, F
• Pintado, ME.
• Santos-Silva, A
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• Fernandes, JC.
• Sereno, J
• Garrido, P
• Parada, B
• Cunha, MF. X.
• Reis, F
• Pintado, ME.
• Santos-Silva, A
• [+] on PubMed
• Fernandes, JC.
• Sereno, J
• Garrido, P
• Parada, B
• Cunha, MF. X.
• Reis, F
• Pintado, ME.
• Santos-Silva, A

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Mar. Drugs 2012, 10(12), 2661-2675; doi:10.3390/md10122661

Article

Inhibition of Bladder Tumor Growth by Chitooligosaccharides in an Experimental Carcinogenesis Model

João C. Fernandes ^1,2,3,* , José Sereno ² , Patricia Garrido ² , Belmiro Parada ⁴ , Maria F. X. Cunha ⁵ , Flávio Reis ² , Manuela E. Pintado ³  and Alice Santos-Silva ^1,6

¹ Institute for Molecular and Cellular Biology, Porto University, Porto 4150-180, Portugal ² Institute of Pharmacology & Experimental Therapeutics, IBILI, Medicine Faculty, Coimbra University, Coimbra 3000-548, Portugal ³ CBQF/Biotechnology School, Portuguese Catholic University, Porto 4200-072, Portugal ⁴ Department of Urology & Renal Transplantation, Coimbra University Hospital, Coimbra 3000-075, Portugal ⁵ Service of Anatomic Pathology, Coimbra University Hospital, Coimbra 3000-075, Portugal ⁶ Department of Biochemistry, Pharmacy Faculty, Porto University, Porto 4050-313, Portugal

* Author to whom correspondence should be addressed.

Received: 3 September 2012; in revised form: 8 October 2012 / Accepted: 8 November 2012 / Published: 26 November 2012

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Abstract: Urinary bladder cancer is one of the most common cancers worldwide, with the highest incidence in industrialized countries. Patients with cancer commonly use unconventional and complementary therapy including nutraceuticals. In this study we evaluated the efficacy of chitooligosaccharides (in orange juice) in rat bladder cancer chemoprevention and as therapeutic agent, on a rat model of urinary bladder carcinogenesis induced with N-butyl-N-(4-hydroxybutyl) nitrosamine. Results indicate that chitooligosaccharides may have a preventive effect on bladder cancer development and a curative effect upon established bladder tumors, dependent on the concentration ingested 500 mg/kg b.w., every three days, showed capacity to inhibit and prevent the proliferation of bladder cancer; however, this was associated with secondary effects such as hypercholesterolemia and hypertriglyceridemia. The use of lower doses (50 and 250 mg/kg b.w.) showed only therapeutic effects. It is further suggested that this antitumor effect might be due to its expected anti-inflammatory action, as well as by mechanisms not directly dependent of COX-2 inhibition, such as cellular proliferation control and improvement in antioxidant profile.

Keywords: chitosans; bladder cancer; chemoprevention; chitooligosaccharides

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