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Dual mechanisms for telomerase inhibition in DLD‐1 human colorectal adenocarcinoma cells by polyunsaturated fatty acids
Author(s) -
Eitsuka Takahiro,
Nakagawa Kiyotaka,
Miyazawa Teruo
Publication year - 2004
Publication title -
biofactors
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.204
H-Index - 94
eISSN - 1872-8081
pISSN - 0951-6433
DOI - 10.1002/biof.552210105
Subject(s) - telomerase , telomerase reverse transcriptase , polyunsaturated fatty acid , biochemistry , chemistry , enzyme , colorectal adenocarcinoma , cell culture , fatty acid , microbiology and biotechnology , biology , adenocarcinoma , gene , cancer , genetics
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.