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Induction of medulloblastoma cell apoptosis by sulforaphane, a dietary anticarcinogen from Brassica vegetables.

Abstract
There is increasing evidence that a variety of natural substances derived from the diet may act as potent chemopreventive agents. In this work, we show that DAOY cells, a widely used model of metastatic medulloblastoma (MBL), are highly sensitive to sulforaphane, a naturally occurring isothiocyanate from Brassica vegetables. Sulforaphane induced DAOY cell death by apoptosis, as determined by DNA fragmentation and chromatin condensation. DAOY apoptosis correlates with the induction of caspase-3 and -9 activities, resulting in the cleavage of PARP and vimentin. Both the cytotoxic effect and apoptotic characteristics induced by sulforaphane were reversed by zVAD-fmk, a broad spectrum caspase inhibitor, demonstrating the important role of caspases in its cytotoxic effect. These results identify sulforaphane as a novel inducer of MBL cell apoptosis, supporting the potential clinical usefulness of diet-derived substances as chemopreventive agents.
AuthorsDenis Gingras, Martin Gendron, Dominique Boivin, Albert Moghrabi, Yves Théorêt, Richard Béliveau
JournalCancer letters (Cancer Lett) Vol. 203 Issue 1 Pg. 35-43 (Jan 08 2004) ISSN: 0304-3835 [Print] Ireland
PMID14670615 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anticarcinogenic Agents
  • Isothiocyanates
  • Proteins
  • Sulfoxides
  • Thiocyanates
  • Vimentin
  • CASP3 protein, human
  • CASP9 protein, human
  • Caspase 3
  • Caspase 9
  • Caspases
  • sulforaphane
Topics
  • Animals
  • Anticarcinogenic Agents (pharmacology)
  • Apoptosis (drug effects)
  • Caspase 3
  • Caspase 9
  • Caspases (metabolism)
  • Cattle
  • DNA Fragmentation
  • HL-60 Cells
  • Humans
  • Isothiocyanates
  • Medulloblastoma (enzymology, prevention & control)
  • Neoplasm Metastasis (prevention & control)
  • Proteins (metabolism)
  • Sulfoxides
  • Thiocyanates (pharmacology)
  • Tumor Cells, Cultured
  • Vegetables (chemistry)
  • Vimentin (metabolism)

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