التفاصيل البيبلوغرافية
| العنوان: |
6- and 8-Prenylnaringenin, Novel Natural Histone Deacetylase Inhibitors Found in Hops, Exert Antitumor Activity on Melanoma Cells. |
| المؤلفون: |
Venturelli, Sascha, Niessner, Heike, Sinnberg, Tobias, Berger, Alexander, Burkard, Markus, Urmann, Corinna, Donaubauer, Kathrin, Böcker, Alexander, Leischner, Christian, Riepl, Herbert, Frank, Jan, Lauer, Ulrich M., Garbe, Claus, Busch, Christian |
| المصدر: |
Cellular Physiology & Biochemistry (Karger AG); 2018, Vol. 51 Issue 2, p543-556, 14p |
| مصطلحات موضوعية: |
MELANOMA, HISTONE deacetylase inhibitors, ANTINEOPLASTIC agents, CANCER cells, ACETYLATION |
| مستخلص: |
Background/Aims: Prenylnaringenins are natural prenylflavonoids with anticancer properties. However, the underlying mechanisms have not been elucidated yet. Here we report a novel mode of action of 6- and 8-prenylnaringenin (PN) on human melanoma cells: Inhibition of cellular histone deacetylases (HDACs). Methods: We performed in silico and in vitro analyses using 6-PN or 8-PN to study a possible interaction of 6-PN or 8-PN with HDAC as well as Western blot and FACS analyses, real-time cell proliferation and cell viability assays to assess the impact of 6-PN and 8-PN on human metastatic melanoma cells. Results: In silico, 6-PN and 8-PN fit into the binding pocket of HDAC2, 4, 7 and 8, binding to the zinc ion of their catalytic center that is essential for enzymatic activity. In vitro, 100 μmol/L of 6-PN or 8-PN inhibited all 11 conserved human HDAC of class I, II and IV. In clinical oncology HDAC inhibitors are currently investigated as new anticancer compounds. In line, treatment of SK-MEL-28 cells with 6-PN or 8-PN induced a hyperacetylation of histone complex H3 within 2 h. Further, 6-PN or 8-PN mediated a prominent, dose-dependent reduction of cellular proliferation and viability of SK-MEL-28 and BLM melanoma cells. This effect was apoptosis-independent and accompanied by down-regulation of mTOR-specific pS6 protein via pERK/pP90 in SK-MEL-28 cells. Conclusion: The identification of a broad inhibitory capacity of 6-PN and 8-PN for HDAC enzymes with antiproliferative effects on melanoma cells opens the perspective for clinical application as novel anti-melanoma drugs and the usage as innovative lead structures for chemical modification to enhance pharmacology or inhibitory activities. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
