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

Pizzimenti, Stefania; Menegatti, Elisa; Berardi, Daniela; Toaldo, Cristina; Pettazzoni, Piergiorgio; Minelli, Rosalba; Giglioni, Barbara; Cerbone, Angelo; Dianzani, Mario U.; Ferretti, Carlo; Barrera, Giuseppina

doi:10.1016/j.jnutbio.2009.06.005

« Previous Next »The Journal of Nutritional Biochemistry
Volume 21, Issue 9 , Pages 818-826, September 2010

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☆

Stefania Pizzimenti
- Department of Medicine and Experimental Oncology, Section of General Pathology, University of Turin, 10125 Torino, Italy
- Corresponding author. Dipartimento di Medicina ed Oncologia Sperimentale, Sezione di Patologia Generale, 10153 Torino, Italy. Tel.: +39 011 6707763; fax: +39 011 6707753.
- S.P. and E.M. have contributed equally to the studies present in this manuscript.
Elisa Menegatti
- Department of Experimental Medicine and Oncology, Section of Clinical Pathology, University of Turin, 10125 Torino, Italy
- S.P. and E.M. have contributed equally to the studies present in this manuscript.
Daniela Berardi
- Department of Experimental Medicine and Oncology, Section of Clinical Pathology, University of Turin, 10125 Torino, Italy
Cristina Toaldo
- Department of Medicine and Experimental Oncology, Section of General Pathology, University of Turin, 10125 Torino, Italy
Piergiorgio Pettazzoni
- Department of Medicine and Experimental Oncology, Section of General Pathology, University of Turin, 10125 Torino, Italy
Rosalba Minelli
- Department of Medicine and Experimental Oncology, Section of General Pathology, University of Turin, 10125 Torino, Italy
Barbara Giglioni
- Institute of Molecular Bioimaging and Physiology (IBFM), National Research Council (CNR), 20090 Segrate (Milano), Italy
Angelo Cerbone
- Department of Medicine and Experimental Oncology, Section of General Pathology, University of Turin, 10125 Torino, Italy
Mario U. Dianzani
- Department of Medicine and Experimental Oncology, Section of General Pathology, University of Turin, 10125 Torino, Italy
Carlo Ferretti
- Department of Anatomy, Pharmacology and Forensic Medicine, University of Turin, 10125 Torino, Italy.
Giuseppina Barrera
- Department of Medicine and Experimental Oncology, Section of General Pathology, University of Turin, 10125 Torino, Italy

Received 20 March 2009; received in revised form 8 June 2009; accepted 15 June 2009. published online 04 September 2009.

Abstract

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 μM), 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.

Keywords: 4-Hydroxynonenal, Caco-2, HT-29, Telomerase activity, hTERT gene expression, GSH, Myc/Mad/Max network