Stimulation of suicidal erythrocyte death by sulforaphane

Basic Clin Pharmacol Toxicol. 2015 Mar;116(3):229-35. doi: 10.1111/bcpt.12309. Epub 2014 Oct 7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Annexin A5 / metabolism
  • Anticarcinogenic Agents / administration & dosage
  • Anticarcinogenic Agents / pharmacology*
  • Apoptosis / drug effects
  • Calcium / metabolism
  • Cell Death / drug effects*
  • Cell Size / drug effects
  • Ceramides / metabolism
  • Dose-Response Relationship, Drug
  • Erythrocytes / drug effects*
  • Erythrocytes / metabolism
  • Humans
  • Isothiocyanates / administration & dosage
  • Isothiocyanates / pharmacology*
  • Phosphatidylserines / metabolism

Substances

  • Annexin A5
  • Anticarcinogenic Agents
  • Ceramides
  • Isothiocyanates
  • Phosphatidylserines
  • sulforafan
  • Calcium