title: Aloe emodin inhibits the cytotoxic action of tumor necrosis factor.
abstract: We demonstrate the capacity of an herbal anthraquinone aloe emodin to reduce the cytotoxicity of the proinflammatory cytokine tumor necrosis factor (TNF) towards L929 mouse fibrosarcoma and U251 human glioma cell lines. Aloe emodin inhibited both TNF-induced cell necrosis and apoptosis, but it did not reduce cell death induced by UV radiation or hydrogen peroxide. Aloe emodin inhibited both basal and TNF-triggered activation of extracellular signal-regulated kinase (ERK), and a selective blockade of ERK activation mimicked the cytoprotective action of the drug. On the other hand, aloe emodin did not affect TNF-induced activation of p38 mitogen-activated protein kinase or generation of reactive oxygen species. The combination of aloe emodin and TNF caused an intracellular appearance of acidified autophagic vesicles, and the inhibition of autophagy with bafilomycin or 3-methyladenine efficiently blocked the cytoprotective action of aloe emodin. These data indicate that aloe emodin could prevent TNF-triggered cell death through mechanisms involving induction of autophagy and blockade of ERK activation.
authors.affiliation: Institute for Biological Research, Department of Immunology, Belgrade, Serbia and Montenegro.
authors.forename: Ljubica
authors.initials: L
authors.lastname: Harhaji
authors.forename: Sanja
authors.initials: S
authors.lastname: Mijatovic
authors.forename: Danijela
authors.initials: D
authors.lastname: Maksimovic-Ivanic
authors.forename: Dusan
authors.initials: D
authors.lastname: Popadic
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Isakovic
authors.forename: Biljana
authors.initials: B
authors.lastname: Todorovic-Markovic
authors.forename: Vladimir
authors.initials: V
authors.lastname: Trajkovic
mesh_terms: D000818:Animals; D000880:Anthraquinones; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004642:Emodin / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009336:Necrosis / Q000188:drug therapy; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D000079424:Tumor Necrosis Factor Inhibitors; D048069:Tumor Necrosis Factors / Q000494:pharmacology*
chemical_list: D000880:Anthraquinones; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D000079424:Tumor Necrosis Factor Inhibitors; D048069:Tumor Necrosis Factors; C518327:aloe emodin; D020928:Mitogen-Activated Protein Kinases; D004642:Emodin