As high
telomerase activity is detected in most
cancer cells,
telomerase represents a promising
cancer therapeutic target. We investigated the inhibitory effect of various
fatty acids on
telomerase, with particular emphasis on those with antitumor properties, such as
eicosapentaenoic acid (EPA) and
docosahexaenoic acid (DHA). To evaluate the direct effect of
fatty acids on
telomerase, cell lysates of DLD-1 human colorectal
adenocarcinoma cells were mixed with sample
fatty acids, and the
telomerase activity was determined.
Saturated fatty acids and
trans-fatty acids showed very weak or no inhibition of
telomerase. In contrast, cis-
unsaturated fatty acids significantly inhibited the
enzyme, and the inhibitory potency was elevated with an increase in the number of double bonds. Accordingly,
polyunsaturated fatty acids (PUFAs), like EPA and DHA, appeared to be powerful
telomerase inhibitors. To assess the transcriptional effect, DLD-1 cells were cultured in the presence of sample
fatty acids, and
telomerase activity and gene expression were subsequently evaluated. Culturing DLD-1 cells with either EPA or DHA resulted in a remarkable decrease in
telomerase activity. EPA and DHA inhibited
telomerase by down-regulating human
telomerase reverse transcriptase (hTERT) and c-myc expression via
protein kinase C inhibition. These results indicate that PUFAs can directly inhibit the enzymatic activity of
telomerase as well as modulate the
telomerase at the transcriptional level.