Herz, Corinna and Hoai Thi Thu Tran, and Landerer, Steffen and Gaus, Johanna and Schlotz, Nina and Lehr, Lia and Schaefer, Wolfgang R. and Treeck, Oliver and Odongo, Grace Akinyi and Skatchkov, Ivan and Lamy, Evelyn (2017) Normal human immune cells are sensitive to telomerase inhibition by Brassica-derived 3,3-diindolylmethane,partly mediated via ER alpha/beta-AP1 signaling. MOLECULAR NUTRITION & FOOD RESEARCH, 61 (9): 1600524. ISSN 1613-4125, 1613-4133
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | BREAST-CANCER CELLS; GENE-EXPRESSION; PROSTATE-CANCER; DIETARY INDOLE-3-CARBINOL; LYMPHOCYTE DEVELOPMENT; ENDOMETRIAL CANCER; ESTROGEN-RECEPTORS; ANTICANCER AGENT; DOWN-REGULATION; HEPG2 CELLS; 3,3-diindolylmethane; ER-AP-1 signal transduction; Phytoestrogens; Safety of phytochemicals; Telomerase |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Frauenheilkunde und Geburtshilfe (Schwerpunkt Frauenheilkunde) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 13:15 |
| Last Modified: | 12 Feb 2019 15:10 |
| URI: | https://pred.uni-regensburg.de/id/eprint/1309 |
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