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

• Published in: Cancer letters Vol. 203; no. 1; pp. 35 - 43
• Main Authors: Gingras, Denis, Gendron, Martin, Boivin, Dominique, Moghrabi, Albert, Théorêt, Yves, Béliveau, Richard
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 08.01.2004; Elsevier Limited
• Subjects: Animals; Anticarcinogenic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Brain cancer; Brassica vegetables; Caspase 3; Caspase 9; Caspases - metabolism; Cattle; DNA Fragmentation; HL-60 Cells; Humans; Isothiocyanates; Kinases; Medical research; Medulloblastoma; Medulloblastoma - enzymology; Medulloblastoma - prevention & control; Neoplasm Metastasis - prevention & control; Proteins - metabolism; Sulforaphane; Thiocyanates - pharmacology; Tumor Cells, Cultured; Vegetables; Vegetables - chemistry; Vimentin - metabolism; zVAD-fmk, z-Val-Ala-Asp(OMe)-fluoromethylketone; TUNEL, terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling; PBS, phosphate-buffered saline; TNFα, tumor necrosis factor-alpha; DAPI, 4′,6-diamino-2-phenylindole dihydrochloride; PAGE, polyacrylamide gel electrophoresis; Sulforaphane; Medulloblastoma; rfu, relative fluorescence unit; Brassica vegetables; PARP, poly(ADP-ribose) polymerase; Apoptosis; PEITC, phenylethyl isothiocyanate
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2003.08.025

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.