title: Stimulation of suicidal erythrocyte death by sulforaphane.
abstract: Sulforaphane, an isothiocyanate from cruciferous vegetable, counteracts malignancy. The effect is at least in part due to the stimulation of suicidal death or apoptosis of tumour cells. Mechanisms invoked in sulforaphane-induced apoptosis include mitochondrial depolarization and altered gene expression. Despite the lack of mitochondria and nuclei, erythrocytes may, similar to apoptosis of nucleated cells, enter eryptosis, a suicidal cell death characterized by cell shrinkage and phosphatidylserine translocation to the erythrocyte surface. Stimulators of eryptosis include increase of cytosolic Ca(2+)-activity ([Ca(2+)]i). This study explored whether sulforaphane stimulates eryptosis. Cell volume was estimated from forward scatter, phosphatidylserine exposure at the cell surface from annexin V binding and [Ca(2+)]i from Fluo-3 fluorescence. A 48-hr treatment of human erythrocytes with sulforaphane (50-100 μM) significantly decreased forward scatter, significantly increased the percentage of annexin V binding cells and significantly increased [Ca(2+)]i. The effect of sulforaphane (100 μM) on annexin V binding was significantly blunted but not abrogated by the removal of extracellular Ca(2+). Sulforaphane (100 μM) significantly increased ceramide formation. In conclusion, sulforaphane stimulates suicidal erythrocyte death or eryptosis, an effect at least partially, but not exclusively, due to the stimulation of Ca(2+) entry and ceramide formation.
authors.affiliation: Department of Physiology, University of Tübingen, Tuebingen, Germany.
authors.forename: Kousi
authors.initials: K
authors.lastname: Alzoubi
authors.forename: Salvatrice
authors.initials: S
authors.lastname: Calabrò
authors.forename: Caterina
authors.initials: C
authors.lastname: Faggio
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D017304:Annexin A5 / Q000378:metabolism; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects*; D048429:Cell Size / Q000187:drug effects; D002518:Ceramides / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D017879:Isothiocyanates / Q000008:administration & dosage / Q000494:pharmacology*; D010718:Phosphatidylserines / Q000378:metabolism; D013454:Sulfoxides
chemical_list: D017304:Annexin A5; D016588:Anticarcinogenic Agents; D002518:Ceramides; D017879:Isothiocyanates; D010718:Phosphatidylserines; D013454:Sulfoxides; C016766:sulforaphane; D002118:Calcium