Berger, Alexander and Venturelli, Sascha and Kallnischkies, Mascha and Boecker, Alexander and Busch, Christian and Weiland, Timo and Noor, Seema and Leischner, Christian and Weiss, Thomas S. and Lauer, Ulrich M. and Bischoff, Stephan C. and Bitzer, Michael (2013) Kaempferol, a new nutrition-derived pan-inhibitor of human histone deacetylases. JOURNAL OF NUTRITIONAL BIOCHEMISTRY, 24 (6). pp. 977-985. ISSN 0955-2863,
Full text not available from this repository. (Request a copy)Abstract
Kaempferol is a natural polyphenol belonging to the group of flavonoids. Different biological functions like inhibition of oxidative stress in plants or animal cells and apoptosis induction have been directly associated with kaempferol. The underlying mechanisms are only partially understood. Here we report for the first time that kaempferol has a distinct epigenetic activity by inhibition of histone deacetylases (HDACs). In silico docking analysis revealed that it fits into the binding pocket of HDAC2, 4, 7 or 8 and thereby binds to the zinc ion of the catalytic center. Further in vitro profiling of all conserved human HDACs of class I, II and IV showed that kaempferol inhibited all tested HDACs. In clinical oncology, HDAC inhibitors are currently under investigation as new anticancer compounds. Therefore, we studied the effect of kaempferol on human-derived hepatoma cell lines HepG2 and Hep3B as well as on HCT-116 colon cancer cells and found that it induces hyperacetylation of histone complex H3. Furthermore, kaempferol mediated a prominent reduction of cell viability and proliferation rate. Interestingly, toxicity assays revealed signs of relevant cellular toxicity in primary human hepatocytes only starting at 50 mu M as well as in an in vivo chicken embryotoxicity assay at 200 mu M. In conclusion, the identification of a novel broad inhibitory capacity of the natural compound kaempferol for human-derived HDAC enzymes opens up the perspective for clinical application in both tumor prevention and therapy. Moreover, kaempferol may serve as a novel lead structure for chemical optimization of pharmacokinetics, pharmacology or inhibitory activities. (C) 2013 Elsevier Inc. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ANTIOXIDANT ACTIVITY; INDUCED APOPTOSIS; CARCINOMA-CELLS; CHICK-EMBRYO; CANCER-CELLS; FLAVONOIDS; CYTOTOXICITY; ACTIVATION; EXTRACT; AGENTS; Kaempferol; Polyphenol; Flavonoid; Histone deacetylase; Epigenetics |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Kinder- und Jugendmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Apr 2020 08:44 |
| Last Modified: | 08 Apr 2020 08:44 |
| URI: | https://pred.uni-regensburg.de/id/eprint/16575 |
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