Down-regulation of telomerase activity in DLD-1 human colorectal adenocarcinoma cells by tocotrienol.
As high telomerase activity is detected in most cancer cells, inhibition of telomerase by drug or dietary food components is a new strategy for cancer prevention. Here, we investigated the inhibitory effect of vitamin E, with particular emphasis on tocotrienol (unsaturated vitamin E), on human telomerase in cell-culture study. As results, tocotrienol inhibited telomerase activity of DLD-1 human colorectal adenocarcinoma cells in time- and dose-dependent manner, interestingly, with delta-tocotrienol exhibiting the highest inhibitory activity. Tocotrienol inhibited protein kinase C activity, resulting in down-regulation of c-myc and human telomerase reverse transcriptase (hTERT) expression, thereby reducing telomerase activity. In contrast to tocotrienol, tocopherol showed very weak telomerase inhibition. These results provide novel evidence for the first time indicating that tocotrienol acts as a potent candidate regulator of telomerase and supporting the anti-proliferative function of tocotrienol.
Eitsuka
Takahiro
T
Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555, Japan.
Nakagawa
Kiyotaka
K
Miyazawa
Teruo
T
D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology; D000975:Antioxidants / Q000494:pharmacology; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000201:enzymology; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors; D019098:Telomerase / Q000037:antagonists & inhibitors*; D024508:Tocotrienols / Q000494:pharmacology*
D000975:Antioxidants; D004268:DNA-Binding Proteins; D016271:Proto-Oncogene Proteins c-myc; D024508:Tocotrienols; D019098:Telomerase