title: Neem leaf extract induces radiosensitization in human neuroblastoma xenograft through modulation of apoptotic pathway.
abstract: Induction of apoptosis is directly correlated with the biological effectiveness of ionizing radiation (IR). Accordingly, we investigated the efficacy of neem leaf extract (NLE) on IR-associated apoptotic transcriptional modulation and cell death in neuroblastoma (NB).
  
  
  METHODS
  NB xenografts exposed to single dose (SDR, 10 Gy) or fractionated (FIR, 2 Gy/d×5d) with or without NLE were examined for transcriptional activation of 84 apoptotic pathway genes using quantitative polymerase chain reaction. Apoptosis was measured using TdT nick-end labeling.
  
  
  RESULTS
  FIR induced 55 and suppressed 10 genes, while SDR induced 49 and suppressed 5 genes. Of these, 46 and 4 genes were commonly up/down-regulated after FIR and SDR. NLE inhibited IR-induced NAIP, BIRC6, BIRC8, NOL3 and enhanced BAK1, BAX, BCL10, CASP1, CASP10 CARD8 and CRADD. Furthermore, NLE conferred FIR- and SDR-induced cell death.
  
  
  CONCLUSIONS
  These data imply that NLE may exert radiosensitization by activating pro-apoptotic signaling and negating survival signaling and may thus potentiate radiotherapy in NB.
authors.affiliation: Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors.forename: Jamunarani
authors.initials: J
authors.lastname: Veeraraghavan
authors.forename: Sheeja
authors.initials: S
authors.lastname: Aravindan
authors.forename: Mohan
authors.initials: M
authors.lastname: Natarajan
authors.forename: Vibhudutta
authors.initials: V
authors.lastname: Awasthi
authors.forename: Terence S
authors.initials: TS
authors.lastname: Herman
authors.forename: Natarajan
authors.initials: N
authors.lastname: Aravindan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D031601:Azadirachta / Q000737:chemistry*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009447:Neuroblastoma / Q000188:drug therapy / Q000473:pathology*; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D012333:RNA, Messenger / Q000235:genetics; D011839:Radiation, Ionizing; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D010936:Plant Extracts; D012333:RNA, Messenger; D011838:Radiation-Sensitizing Agents