title: Valproic acid promotes radiosensitization in meningioma stem-like cells.
abstract: Although meningioma stem-like cells have been isolated and characterized, their therapeutic targeting remains a challenge. Meningioma sphere cells (MgSCs) with cancer stem cells properties show chemo- and radioresistance in comparison with meningioma adherent cells (MgACs). We tested the effect of valproic acid (VPA), a commonly used anti-epileptic drug, which passes the blood brain barrier, on cultured MgSCs. VPA reduced the viability of MgSCs and MgACs. In MgSCs, treatment with VPA increased radio-sensitivity, expression of p-cdc2, p-H2AX and cleaved caspase-3 and PARP. Anchorage-independent growth (AIG) was reduced by VPA. AIG was further reduced by combined treatment with irradiation. Expression of a stem cell marker, Oct4, was reduced by VPA. Oct4 was further decreased by combined treatment with irradiation. These results suggest that VPA may be a potential treatment for meningioma through targeting meningioma stem-like cells.
authors.affiliation: Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, R.O.C.
authors.forename: Hsin-Ying Clair
authors.initials: HY
authors.lastname: Chiou
authors.affiliation: Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan, R.O.C.
authors.forename: Wen-Kuo
authors.initials: WK
authors.lastname: Lai
authors.affiliation: Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan, R.O.C.
authors.forename: Li-Chun
authors.initials: LC
authors.lastname: Huang
authors.affiliation: Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan, R.O.C.
authors.forename: Shih-Ming
authors.initials: SM
authors.lastname: Huang
authors.affiliation: Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan, R.O.C.
authors.forename: Sheau-Huei
authors.initials: SH
authors.lastname: Chueh
authors.affiliation: Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, R.O.C.
authors.forename: Hsin-I
authors.initials: HI
authors.lastname: Ma
authors.affiliation: Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, R.O.C.|Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan, R.O.C.
authors.forename: Dueng-Yuan
authors.initials: DY
authors.lastname: Hueng
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000528:radiation effects; D002454:Cell Differentiation / Q000187:drug effects / Q000528:radiation effects; D015536:Down-Regulation / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D008579:Meningioma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000528:radiation effects*; D050814:Octamer Transcription Factor-3 / Q000096:biosynthesis; D011836:Radiation Tolerance / Q000187:drug effects; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D014635:Valproic Acid
keywords: Oct4; meningioma; radiosensitization; tumor stem-like cells; valproic acid