title: The NFκB inhibitor, SN50, induces differentiation of glioma stem cells and suppresses their oncogenic phenotype.
abstract: The malignant phenotype of glioblastoma multiforme (GBM) is believed to be largely driven by glioma stem-like cells (GSCs), and targeting GSCs is now considered a promising new approach to treatment of this devastating disease. Here, we show that SN50, a cell-permeable peptide inhibitor of NFκB, induced robust differentiation of human GSCs, causing loss of their oncogenic potential. We observed that following treatment of GSCs with SN50, their differentiated progeny cells showed significant decreases in their capability to form neuro-spheres and to invade in vitro and a reduction in their tumorigenicity in mouse xenograft models, but had increased sensitivity to the chemotherapeutic drug temozolomide and to radiation treatment. These results suggest that blocking the NFκB pathway may be explored as a useful mean to induce differentiation of GSCs, and provide another supportive evidence for the promise of differentiation therapy in treatment of malignant brain tumors.
authors.affiliation: Department of Pharmacology; College of Pharmaceutical Sciences; Soochow University; Suzhou, PR China; Department of Pharmacology; The Penn State Hershey Cancer Institute; The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center; Hershey, PA USA.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology; The Penn State Hershey Cancer Institute; The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center; Hershey, PA USA.
authors.forename: Xingcong
authors.initials: X
authors.lastname: Ren
authors.affiliation: Department of Pharmacology; The Penn State Hershey Cancer Institute; The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center; Hershey, PA USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Experimental Therapeutics; MD Anderson Cancer Center; Houston, TX USA.
authors.forename: Xiuping
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Medicine; The Penn State Hershey Cancer Institute; The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center; Hershey, PA USA.
authors.forename: Joshua E
authors.initials: JE
authors.lastname: Allen
authors.affiliation: Department of Pharmacology; College of Pharmaceutical Sciences; Soochow University; Suzhou, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology; The Penn State Hershey Cancer Institute; The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center; Hershey, PA USA.
authors.forename: Yunsheng
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Pharmacology; The Penn State Hershey Cancer Institute; The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center; Hershey, PA USA.
authors.forename: Siu-Yuan
authors.initials: SY
authors.lastname: Huang
authors.affiliation: Department of Neuro-Oncology; MD Anderson Cancer Center; Houston, TX USA.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Public Health Sciences; The Penn State Hershey Cancer Institute; The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center; Hershey, PA USA.
authors.forename: Arthur
authors.initials: A
authors.lastname: Berg
authors.affiliation: Department of Neurosurgery; The Penn State Hershey Cancer Institute; The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center; Hershey, PA USA.
authors.forename: Becky S
authors.initials: BS
authors.lastname: Webb
authors.affiliation: Department of Neurosurgery; The Penn State Hershey Cancer Institute; The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center; Hershey, PA USA.
authors.forename: James
authors.initials: J
authors.lastname: Connor
authors.affiliation: Department of Experimental Therapeutics; MD Anderson Cancer Center; Houston, TX USA.
authors.forename: Chang-Gong
authors.initials: CG
authors.lastname: Liu
authors.affiliation: Department of Neuro-Oncology; MD Anderson Cancer Center; Houston, TX USA.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Department of Medicine; The Penn State Hershey Cancer Institute; The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center; Hershey, PA USA.
authors.forename: Wafik S
authors.initials: WS
authors.lastname: El-Deiry
authors.affiliation: Department of Pharmacology; College of Pharmaceutical Sciences; Soochow University; Suzhou, PR China; Department of Pharmacology; The Penn State Hershey Cancer Institute; The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center; Hershey, PA USA.
authors.forename: Jin-Ming
authors.initials: JM
authors.lastname: Yang
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy; D002454:Cell Differentiation / Q000187:drug effects*; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D005786:Gene Expression Regulation; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy; D064593:Heterografts; D006801:Humans; D008819:Mice, Nude; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D010455:Peptides / Q000494:pharmacology* / Q000627:therapeutic use; D000077204:Temozolomide; D014407:Tumor Cells, Cultured
chemical_list: D018906:Antineoplastic Agents, Alkylating; D016328:NF-kappa B; D010455:Peptides; C118258:SN50 peptide; D003606:Dacarbazine; D000077204:Temozolomide
keywords: NFκB inhibitor; SN50; brain tumor; differentiation; glioma stem cells