The effects of poly
unsat
urated fatty acids (PUFAs) obtained from the diet on colorectal cancer have been widely explored. However, controversial res
ults have been obtained abo
ut the role played by the lipid peroxidation prod
ucts of PUFAs, s
uch 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 st
udied the effects of a low dose of HNE (1 μM), similar to those “physiologically” fo
und 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-reg
ulation 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, s
uggesting that the inhibition of telomerase activity co
uld be a general mechanism involved in the antiproliferative effect exerted by this aldehyde. Finally, we el
ucidated the mechanism of hTERT inhibition by HNE. A red
uction of GSH content preceded the decrease of telomerase activity, b
ut this only partially explained the telomerase activity inhibition. The major mechanism of HNE action seems to be the mod
ulation 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.