Dual mechanisms for telomerase inhibition in DLD-1 human colorectal adenocarcinoma cells by polyunsaturated fatty acids.
Polyunsaturated fatty acids (PUFAs) have been reported to have antitumor activity. In this study, we have tested whether telomerase might be a target for the antitumor effect of fatty acids using DLD-1 colorectal adenocarcinoma cells. In a cell-free approach, fatty acids were added directly to cell lysates, and we confirmed that increasing fatty acid unsaturation correlates with increased inhibition of telomerase activity. Using a cell culture approach, DLD-1 cells were cultured with fatty acids. In a time and dose dependent manner, EPA and DHA suppressed cellular telomerase activity and the mRNAs encoding hTERT (human telomerase reverse transcriptase) and c-myc. Based on these observations, we suggest that PUFAs inhibit telomerase activity through dual mechanisms: direct inhibition of enzymatic activity and down regulation of hTERT, one of the telomerase components.
Eitsuka
Takahiro
T
Food & Biodynamic Chemistry Laboratory, Graduate School of Life Science and Agriculture, Tohoku University, Sendai 981-8555, Japan.
Nakagawa
Kiyotaka
K
Miyazawa
Teruo
T
D000230:Adenocarcinoma / Q000201:enzymology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D002474:Cell-Free System; D015179:Colorectal Neoplasms / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D006801:Humans; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000037:antagonists & inhibitors*
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D005231:Fatty Acids, Unsaturated; D019098:Telomerase