title: Noscapine and diltiazem augment taxol and radiation-induced S-phase arrest and clonogenic death of C6 glioma in vitro.
abstract: BACKGROUND
  Radiation therapy after surgical resection is the approved treatment of gliomas, and survival benefits are reported with taxane-based chemotherapy. We investigated whether these regimes could be augmented with blood-brain barrier permeable drugs, N and D. Noscapine is an opioid antitussive, which acts anti cancer via blocking microtubule dynamics. Diltiazem is a calcium channel-blocking cardiac antiarrythmic, which also blocks tumor growth and P-glycoprotein.
  
  
  METHODS
  Effects of N (11.1 micromol/L), D (11.1 micromol/L), and T (11.7 micromol/L) were monitored in C6 glioma cells via S phase, colony formation, and fine structure analysis.
  
  
  RESULTS
  Taxol depleted S phase from 35.2% to 12.2%. Both N and D synergistically augmented T-mediated S-phase depletion, and they also effectively reduced colonies, which were more potent by N by 49%. Taxol reduced colonies by 98%, and there were almost no surviving colonies in copresence of T with either N or D. Colony reduction by radiotherapy was increased strongly by T and significantly by N. Taxol and radiation profoundly increased number of mitochondria. Both D and N suppressed this increase via myelinosis and autophagy.
  
  
  CONCLUSIONS
  Noscapine and D should be further tested in animal models because of their potential and already-present clinical applicability.
authors.affiliation: Golden Horn (Halic) University, Capa, Istanbul 34390, Turkey. maltinoz@gmail.com
authors.forename: Meric A
authors.initials: MA
authors.lastname: Altinoz
authors.forename: Ayhan
authors.initials: A
authors.lastname: Bilir
authors.forename: Rolando F
authors.initials: RF
authors.lastname: Del Maestro
authors.forename: Sevilcan
authors.initials: S
authors.lastname: Tuna
authors.forename: Emin
authors.initials: E
authors.lastname: Ozcan
authors.forename: Gunduz
authors.initials: G
authors.lastname: Gedikoglu
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D045744:Cell Line, Tumor; D004110:Diltiazem / Q000494:pharmacology*; D004357:Drug Synergism; D005910:Glioma / Q000188:drug therapy* / Q000532:radiotherapy; D006801:Humans; D008854:Microscopy, Electron; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009665:Noscapine / Q000494:pharmacology*; D017239:Paclitaxel / Q000494:pharmacology*; D016196:S Phase / Q000187:drug effects* / Q000528:radiation effects; D014410:Tumor Stem Cell Assay
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D009665:Noscapine; D004110:Diltiazem; D017239:Paclitaxel