title: Overexpression of SSAT by DENSPM treatment induces cell detachment and             apoptosis in glioblastoma.
abstract: N1,N11-diethylnorspermine (DENSPM), a polyamine analog that induces expression             of spermidine/spermine N1-acetyltransferase (SSAT) and reduces polyamine levels             in eukaryotic cells, has demonstrated anticancer effects in many cancer cell types.             Gene expression of SSAT after treatment with DENSPM was measured in both U87 and             LN229 cells using real-time PCR. Induction of SSAT mRNA using DENSPM resulted             in significantly higher levels in U87 cells than in LN229 cells. Furthermore,             DENSPM caused marked cell detachment in U87 cells and to a lesser extent in LN229             cells. We hypothesized that elevated SSAT expression plays a key role in DENSPM-induced             cell detachment in glioblastoma cells. To investigate whether forced expression             of SSAT would lead to reduced cell adhesion and increased cell detachment, we             transfected a PCMV-SSAT plasmid into LN229 cells and observed significant cell             detachment. In addition, we treated U87 cells with SSAT siRNA together with DENSPM             to blunt the induction of SSAT by DENSPM. This resulted in an inhibition of cell             detachment in U87 cells compared with the DENSPM treatment alone. Increased SSAT             expression by transfection enhanced the DENSPM cell-kill effect in LN229 cells             whereas reduction of SSAT by siRNA attenuated the DENSPM cell-kill effect. The             protein levels of AKT, mTOR and integrin α5β1, which are members of the cell adhesion             and anti-apoptotic signal transduction pathways, were decreased in the PCMV-SSAT             transfected LN229 cells. Collectively, these results demonstrate that SSAT induction             at least partially plays a role in cell detachment and apoptosis of glioblastoma             cells by DENSPM treatment.
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin Neurological Institute, Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, PR China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
authors.forename: Shizhao
authors.initials: S
authors.lastname: Wang
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Jianning
authors.initials: J
authors.lastname: Zhang
authors.forename: Rongcai
authors.initials: R
authors.lastname: Jiang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001932:Brain Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D006801:Humans; D039081:Integrin alpha5beta1 / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D013096:Spermine / Q000031:analogs & derivatives* / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation; D000099228:Diamine N-Acetyltransferase
chemical_list: D000123:Acetyltransferases; D000970:Antineoplastic Agents; D039081:Integrin alpha5beta1; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D013096:Spermine; D058570:TOR Serine-Threonine Kinases; D000099228:Diamine N-Acetyltransferase; C059685:N(1),N(11)-diethylnorspermine; C546842:MTOR protein, human