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Impact of the dietary polyacetylenic falcarinol and falcarindiol on inflammation and colorectal cancer: A mechanistic study in a primed rat model

Abstract

Colorectal cancer (CRC) development is a multistep process,from normal epithelial cells via inflammation to aberrant crypt foci (ACF)and progressive adenoma stages, to carcinomas and then metastatic disease [1, 2]. In order to reduce the incidence and consequences of CRC, effective prevention and treatment strategies need to be identified. Due to thelong precancerous stage of identifiable disease, dietary intervention mayexert favorable effect on polyp formation and/or inhibition of adenomastransformation to CRC. Recent findings indicate that long-term consumption of a diet rich in vegetables may prevent the development of CRC [3].For the prevention of CRC by dietary measures, vegetables such as carrotsare highly interesting due to their content of the bioactive polyacetylenic falcarinol (FaOH) and falcarindiol (FaDOH) [4]. FaOH and FaDOH haveshown many interesting bioactivities including anti-inflammatory and cytotoxic activity [4-6]as well as antineoplastic effect in animal models [7, 8].In this study, we demonstrate that FaOH and FaDOH prevent the development of early neoplastic lesions in the colorectal intestine in a dose-response relationship corresponding to the logarithmic of the concentrationof the contents of FaOH and FaDOH in the diet. Furthermore, the resultspresented also demonstrate that FaOH and FaDOH have an effect on inflammatory markers and they seem to act as selective COX-2 inhibitors,which appears to be their main mechanism of action in relation to coloncancer prophylactics.Colorectal cancer (CRC) development is a multistep process,from normal epithelial cells via inflammation to aberrant crypt foci (ACF)and progressive adenoma stages, to carcinomas and then metastatic disease [1, 2]. In order to reduce the incidence and consequences of CRC, effective prevention and treatment strategies need to be identified. Due to thelong precancerous stage of identifiable disease, dietary intervention mayexert favorable effect on polyp formation and/or inhibition of adenomastransformation to CRC. Recent findings indicate that long-term consumption of a diet rich in vegetables may prevent the development of CRC [3].For the prevention of CRC by dietary measures, vegetables such as carrotsare highly interesting due to their content of the bioactive polyacetylenic falcarinol (FaOH) and falcarindiol (FaDOH) [4]. FaOH and FaDOH haveshown many interesting bioactivities including anti-inflammatory and cytotoxic activity [4-6]as well as antineoplastic effect in animal models [7, 8].In this study, we demonstrate that FaOH and FaDOH prevent the development of early neoplastic lesions in the colorectal intestine in a dose-response relationship corresponding to the logarithmic of the concentrationof the contents of FaOH and FaDOH in the diet. Furthermore, the resultspresented also demonstrate that FaOH and FaDOH have an effect on inflammatory markers and they seem to act as selective COX-2 inhibitors,which appears to be their main mechanism of action in relation to coloncancer prophylactics

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This paper was published in VBN.

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