Abstract
Scope: Indole-3-carbinol (13C) and 3,3'-diindolylmethane (DIM) from Brassica plants are regarded as promising anticancer phytochemicals. The enzyme telomerase is a very attractive target for cancer therapeutics; in normal cells such as lymphocytes, it plays a decisive role for cell maintenance. The effect of 13C and DIM on telomerase in normal human immune cells (PBMC) was studied compared to ...
Abstract
Scope: Indole-3-carbinol (13C) and 3,3'-diindolylmethane (DIM) from Brassica plants are regarded as promising anticancer phytochemicals. The enzyme telomerase is a very attractive target for cancer therapeutics; in normal cells such as lymphocytes, it plays a decisive role for cell maintenance. The effect of 13C and DIM on telomerase in normal human immune cells (PBMC) was studied compared to leukaemia cells (HL-60). Signalling of telomerase regulation via estrogen receptor (ER) was addressed. Methods and results: Short-term treatment with 13C and DIM inhibited telomerase activity in leukaemia cells (>30 mu M 13C; >3 mu M DIM). In CD3/CD28 activated PBMC, inhibition was stronger, though (>3 mu M 13C; >1 mu M DIM). DIM long-term treatment resulted in DNA damage induction and proliferation inhibition in PBMC as determined by the comet assay and CF SE staining, respectively. A relevance of ER alpha/beta-AP1 signaling for telomerase inhibition on enzyme activity, but not transcription level became evident indicating a nonclassical mode for ER regulation of telomerase by DIM. Conclusion: Although desired in cancer cells, this study identified a potential adverse impact of 13C and DIM on telomerase action in normal human immune cells, partly mediated by an ER-dependent mechanism. These new findings should be considered for potential chronic high-dose chemoprevention strategies using these compounds.
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