4-Hydroxynonenal, a lipid peroxidation product of dietary polyunsaturated fatty acids, has anticarcinogenic properties in colon carcinoma cell lines through the inhibition of telomerase activity
Autor: | Giuseppina Barrera, Barbara Giglioni, Stefania Pizzimenti, Rosalba Minelli, Cristina Toaldo, Angelo Cerbone, Piergiorgio Pettazzoni, Mario U. Dianzani, Elisa Menegatti, Carlo Ferretti, Daniela Berardi |
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Rok vydání: | 2010 |
Předmět: |
Telomerase
Endocrinology Diabetes and Metabolism Cellular differentiation Clinical Biochemistry Down-Regulation Gene Expression Apoptosis Biology Biochemistry 4-Hydroxynonenal Lipid peroxidation chemistry.chemical_compound Humans Telomerase reverse transcriptase Molecular Biology Cell Proliferation Aldehydes Nutrition and Dietetics Cell growth Cell Differentiation Glutathione chemistry Caco-2 Cell culture Cancer research Lipid Peroxidation Caco-2 Cells Colorectal Neoplasms HT29 Cells Cell Division |
Zdroj: | The Journal of Nutritional Biochemistry. 21:818-826 |
ISSN: | 0955-2863 |
Popis: | The effects of polyunsaturated fatty acids (PUFAs) obtained from the diet on colorectal cancer have been widely explored. However, controversial results have been obtained about the role played by the lipid peroxidation products of PUFAs, such as 4-hydroxy-nonenal (HNE), in the control of colon cancer growth. This aldehyde, indeed, showed both procarcinogenic and protective effects. In an attempt to verify the action of HNE, we studied the effects of a low dose of HNE (1 microM), similar to those "physiologically" found in normal cells and plasma, on telomerase activity, a key parameter of malignant transformation. Caco-2 cells were exposed to HNE and, paralleling cell growth inhibition, we observed the down-regulation of telomerase activity and hTERT expression. Similar effects have also been observed in HT-29 cells, in which HNE inhibited cell proliferation, telomerase activity and hTERT expression, suggesting that the inhibition of telomerase activity could be a general mechanism involved in the antiproliferative effect exerted by this aldehyde. Finally, we elucidated the mechanism of hTERT inhibition by HNE. A reduction of GSH content preceded the decrease of telomerase activity, but this only partially explained the telomerase activity inhibition. The major mechanism of HNE action seems to be the modulation of expression and activity of transcription factors belonging to the Myc/Mad/Max network. Since the presence of PUFAs in the diet exposes epithelial colon cells to HNE, this aldehyde could contribute to cell growth control through the inhibitory action on telomerase activity and hTERT expression, suggesting a protective effect on colon mucosa. |
Databáze: | OpenAIRE |
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