Inhibition of bladder tumor growth by chitooligosaccharides in an experimental carcinogenesis model.
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.
Institute for Molecular and Cellular Biology, Porto University, Porto 4150-180, Portugal. jfernandes@email.com
João C
JC
Fernandes
José
J
Sereno
Patricia
P
Garrido
Belmiro
B
Parada
Maria F X
MF
Cunha
Flávio
F
Reis
Manuela E
ME
Pintado
Alice
A
Santos-Silva
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D001628:Beverages; D002085:Butylhydroxybutylnitrosamine / Q000633:toxicity; D049109:Cell Proliferation / Q000187:drug effects; D032084:Citrus sinensis / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D009844:Oligosaccharides / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*
D000893:Anti-Inflammatory Agents; D016588:Anticarcinogenic Agents; D009844:Oligosaccharides; D002085:Butylhydroxybutylnitrosamine