Rottlerin inhibits ROS formation and prevents NFkappaB activation in MCF-7 and HT-29 cells.
Rottlerin, a polyphenol isolated from Mallotus Philippinensis, has been recently used as a selective inhibitor of PKC delta, although it can inhibit many kinases and has several biological effects. Among them, we recently found that Rottlerin inhibits the Nuclear Factor kappaB (NFkappaB), activated by either phorbol esters or H(2)O(2). Because of the redox sensitivity of NFkappaB and on the basis of Rottlerin antioxidant property, we hypothesized that Rottlerin could prevent NFkappaB activation acting as a free radicals scavenger, as other natural polyphenols. The current study confirms the antioxidant property of Rottlerin against the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) in vitro and against oxidative stress induced by H(2)O(2) and by menadione in culture cells. We also demonstrate that Rottlerin prevents TNFalpha-dependent NFkappaB activation in MCF-7 cells and in HT-29 cells transfected with the NFkappaB-driven plasmid pBIIX-LUC, suggesting that Rottlerin can inhibit NFkappaB via several pathways and in several cell types.
Maioli
Emanuela
E
Dipartimento di Fisiologia, University of Siena, Italy.
Greci
Lucedio
L
Soucek
Karel
K
Hyzdalova
Martina
M
Pecorelli
Alessandra
A
Fortino
Vittoria
V
Valacchi
Giuseppe
G
D000098:Acetophenones / Q000737:chemistry / Q000494:pharmacology*; D001578:Benzopyrans / Q000737:chemistry / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D016166:Free Radical Scavengers / Q000494:pharmacology; D019073:HT29 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D010851:Picrates / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000098:Acetophenones; D001578:Benzopyrans; D001713:Biphenyl Compounds; D016166:Free Radical Scavengers; D016328:NF-kappa B; D010851:Picrates; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D004247:DNA; D006861:Hydrogen Peroxide; C004931:1,1-diphenyl-2-picrylhydrazyl; C085746:rottlerin