Identification of compounds that induce or repress telomerase activity

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Telomerase activity was regulated by hTERT gene regulation. hTERT promoter (1.8kbp) was cloned into reporter vector which can monitoring hTERT transcription by green fluorescence or luciferase activity. Since normal fibroblasts have limited life span, normal fibroblasts need to be immortalized to using monitoring cells. hTERT gene was infected with retroviruses to immortalized cells. hTERT immortalized normal fibroblasts, NHF-hTERT and MRC-hTERT were used to generate hTERT transcription monitoring cells. We finally generated NHFT-TRP-Luc and MRCT-TRPLuc. We also constructed monitoring cell, RKO-TRPLuc, derived from telomerase positive cancer cells to screening anti-cancer drug targeted hTERT transcription. Using RKO-TRPluc cells, we screened natural compounds which suppress hTERT transcription in cancer cells, and 12 natural products were identified. Among them, two samples showed strong inhibition of hTERT transcription. These two compounds should be powerful anti-cancer activity. Further examination should be necessary to clarify the mechanism of these compounds.