MiR-135a and MRP1 play pivotal roles in the selective lethality of phenethyl isothiocyanate to malignant glioma cells.

摘要: Amounting evidence has demonstrated that phenethyl isothiocyanate (PEITC) is a strong inducer of reactive oxygen species (ROS) and functions as selective killer to various human cancer cells. However, it remains obscure whether PEITC potential lethality malignant glioma Thus in this study, we performed multiple analysis such MTT assay, Hoechst 33258 staining, flow cytometry, foci formation, RT-PCR, Western blot, transfection explore the cells underlying mechanisms. We found induced apoptosis suppressed tumorigenicity migration Furthermore, significantly GSH depletion, ROS production, caspase-9 caspase-3 activation, miR-135a upregulation but not normal Moreover, activated miR-135a-mitochondria dependent pathway by downregulation STAT6, SMAD5 Bcl-xl while Bax expression Cytochrome-C release cell lines immortalized glial HEB Correspondingly, above PEITC-induced activation ROS-MiR-135a-Mitochondria pathways was attenuated pre-transfection with inhibitor, pre-treatment multidrug resistance-associated protein 1 (MRP1) inhibitor Sch B, or combination glutathione (GSH). These results revealed selectively through MRP1-mediated export activate pathway, suggesting application for treating glioma.