title: Sulforaphane-cysteine induces apoptosis by sustained activation of ERK1/2 and caspase 3 in human glioblastoma U373MG and U87MG cells.
abstract: We previously demonstrated that sulforaphane (SFN) inhibited invasion via sustained activation of ERK1/2 in human glioblastoma cells. However, sulforaphane-cysteine (SFN-Cys), an analog of SFN, enriched in plasma with longer half-life, had more potentiality to induce apoptosis. Here we investigated the molecular mechanisms of SFN-Cys-induced apoptosis in human glioblastoma U373MG and U87MG cells. Cell viability assay showed that SFN-Cys inhibited cell viability in a dose-dependent manner. Cell morphology observation also showed SFN-Cys increased the phenotype of cell death in a dose-dependent manner. Furthermore, flow cytometry assay showed that SFN-Cys induced apoptosis significantly in a dose-dependent manner in both cell lines. Furthermore, western blot analysis demonstrated that SFN-Cys induced activation of ERK1/2 in a sustained manner and the activation contributed to upregulation of Bax/Bcl-2 ratio and cleaved caspase 3, and these results can be reversed by the ERK1/2 blocker PD98059. Our results showed that SFN-Cys induced cell apoptosis via sustained activation of ERK1/2 and the ERK1/2 mediated signaling pathways such as activation of caspase 3 and apoptosis-related proteins, thus indicating that SFN-Cys might be a more promising therapeutic agent versus SFN to resist glioblastoma cells, especially in Taxol-resistant cancer cells.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, P.R. China.
authors.forename: Sai
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, P.R. China.
authors.forename: Gaoxiang
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Tian
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Geng
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, P.R. China.
authors.forename: Yabin
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, P.R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Lin
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
mesh_terms: D017209:Apoptosis; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003545:Cysteine / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D017879:Isothiocyanates / Q000737:chemistry / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D013454:Sulfoxides
chemical_list: D005419:Flavonoids; D017879:Isothiocyanates; D013454:Sulfoxides; C505407:CASP3 protein, human; D053148:Caspase 3; C016766:sulforaphane; D003545:Cysteine; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one