Sulforaphane enhances temozolomide-induced apoptosis because of down-regulation of miR-21 via Wnt/β-catenin signaling in glioblastoma.

Temozolomide ( TMZ) has been widely used in the treatment of glioblastoma ( GBM), although inherent or acquired resistance restricts the application. This study was aimed to evaluate the efficacy of sulforaphane ( SFN) to TMZ-induced apoptosis in GBM cells and the potential mechanism. Biochemical assays and subcutaneous tumor establishment were used to characterize the function of SFN in TMZ-induced apoptosis. Our results revealed that β-catenin and miR-21 were concordantly expressed in GBM cell lines, and SFN significantly reduced miR-21 expression through inhibiting the Wnt/β-catenin/ TCF4 pathway. Furthermore, down-regulation of miR-21 enhanced the pro-apoptotic efficacy of TMZ in GBM cells. Finally, we observed that SFN strengthened TMZ-mediated apoptosis in a miR-21-dependent manner. In conclusion, SFN effectively enhances TMZ-induced apoptosis by inhibiting miR-21 via Wnt/β-catenin signaling in GBM cells. These findings support the use of SFN for potential therapeutic approach to overcome TMZ resistance in GBM treatment. [ABSTRACT FROM AUTHOR]