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- Title
Rottlerin: a multifaced regulator of keratinocyte cell cycle.
- Authors
Valacchi, Giuseppe; Pecorelli, Alessandra; Mencarelli, Marzia; Carbotti, Paola; Fortino, Vittoria; Muscettola, Michela; Maioli, Emanuela
- Abstract
In this study we showed that Rottlerin (also called Kamala or Mallotoxin), a natural product purified from Mallotus phillippinensis, is a potent suppressor of human keratinocytes (HaCaT cell line) proliferation. Following Rottlerin treatment, Thymidine incorporation into DNA and re-epithelialisation in a scratch wound model was decreased. At the molecular level, Rottlerin hampered the NFkB activation process, causing loss of cyclin D1 and promoting, in a PKCδ-dependent pathway, ERK activation, which, in turn induced the cell cycle inhibitor p21 Cip1/Kip1. The NFkB-dependent drop in cyclin D1, along with the PKCδ/ERK-dependent induction of p21 Cip1/Kip1, is responsible for growth arrest. These results open the way to further investigation on the Rottlerin therapeutic potential against keratinocyte hyper-proliferative disorders.
- Subjects
KERATINOCYTES; CELL cycle; DNA; CELL lines; PYRIMIDINE nucleotides
- Publication
Experimental Dermatology, 2009, Vol 18, Issue 6, p516
- ISSN
0906-6705
- Publication type
Article
- DOI
10.1111/j.1600-0625.2008.00816.x