Induction of medulloblastoma cell apoptosis by sulforaphane, a dietary anticarcinogen from Brassica vegetables.
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.
Gingras
Denis
D
Centre de Cancérologie Charles-Bruneau, Hôpital Ste-Justine, 3175 Chemin Côte-Ste-Catherine, H3T 1C5 Montréal, Que., Canada.
Gendron
Martin
M
Boivin
Dominique
D
Moghrabi
Albert
A
Théorêt
Yves
Y
Béliveau
Richard
R
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002417:Cattle; D053938:DNA Fragmentation; D018922:HL-60 Cells; D006801:Humans; D017879:Isothiocyanates; D008527:Medulloblastoma / Q000201:enzymology / Q000517:prevention & control*; D009362:Neoplasm Metastasis / Q000517:prevention & control; D011506:Proteins / Q000378:metabolism; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014675:Vegetables / Q000737:chemistry*; D014746:Vimentin / Q000378:metabolism
D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; D011506:Proteins; D013454:Sulfoxides; D013861:Thiocyanates; D014746:Vimentin; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases; C016766:sulforaphane