title: Sulforaphane protects human chondrocytes against cell death induced by various stimuli.
abstract: Chondrocyte cell death can contribute to cartilage degeneration in articular diseases, such as osteoarthritis (OA). Sulforaphane (SFN), a natural compound derived from cruciferous aliment, is well known as an anti-carcinogen, but according to recent evidence it also shows cytoprotective effects on a variety of non-tumoral cells. Therefore we have tested the ability of SFN to protect chondrocytes from cell death in vitro. Treatment of growing monolayer cultures of human C-28/I2 chondrocytes with SFN in the low micro-molecular range for a few days, reduced cell growth without affecting cell survival or inducing apoptosis. However it decreased cell death in C-28/I2 chondrocytes exposed to stimuli previously reported to promptly trigger apoptosis, that is, the cytokine tumor necrosis factor-α (TNF) plus cycloheximide (CHX) or the polyamine analogue N(1),N(11)-diethylnorspermine (DENSPM) plus CHX. In particular pre-treatment with SFN reduced effector and initiator caspase activities and the associated activation of JNK kinases. SFN exerted a cytoprotective action even versus H(2)O(2) , which differently from the previous stimuli induced cell death without producing an evident caspase activation. SFN pre-treatment also prevented caspase activation in three-dimensional micromass cultures of OA chondrocytes stimulated with growth-related oncogene α (GROα), a pro-apoptotic chemokine. The suppression of caspase activation in micromasses appeared to be related to the inhibition of p38 MAPK phosphorylation. In conclusion, the present work shows that low micro-molecular SFN concentrations exert pro-survival and anti-apoptotic actions and influence signaling pathways in a variety of experimental conditions employing chondrocyte cell lines and OA chondrocytes treated with a range of death stimuli.
authors.affiliation: Dipartimento di Biochimica G. Moruzzi, University of Bologna, Bologna, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Facchini
authors.forename: Ivana
authors.initials: I
authors.lastname: Stanic
authors.forename: Silvia
authors.initials: S
authors.lastname: Cetrullo
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Borzì
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Filardo
authors.forename: Flavio
authors.initials: F
authors.lastname: Flamigni
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D054360:Chemokine CXCL1 / Q000633:toxicity; D019902:Chondrocytes / Q000187:drug effects* / Q000473:pathology; D003513:Cycloheximide / Q000633:toxicity; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D017879:Isothiocyanates; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D013096:Spermine / Q000031:analogs & derivatives / Q000633:toxicity; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D054360:Chemokine CXCL1; D017879:Isothiocyanates; D013454:Sulfoxides; D013861:Thiocyanates; D014409:Tumor Necrosis Factor-alpha; C059685:N(1),N(11)-diethylnorspermine; D013096:Spermine; D003513:Cycloheximide; D006861:Hydrogen Peroxide; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020169:Caspases; C016766:sulforaphane