title: An in vitro study on the effect of vinca alkaloid, vinorelbine, on chromatin histone, HMGB proteins and induction of apoptosis in mice non-adherent bone marrow cells.
abstract: BACKGROUND
  Vinoreline is a vinca alkaloid anticancer drug widely used in cancer therapy. Drugs are not target specific, therefore might affect normal tissues/cells, in which bone marrow is the important one.
  
  
  OBJECTIVE
  To elucidate the cytotoxic and genotoxic effect of vinca alkaloid anti cancer drug, vinorelbine, on mice non-adherent bone marrow cells in vitro.
  
  
  METHODS
  Non-adherent bone marrow cells were isolated and exposed to various concentrations (0-160 µg/ml) for 4 h at 23 °C. The chromatin proteins were analyzed by SDS PAGE and western blot. Fluorescent dye staining of the cells, anion superoxide and DNA fragmentations assays were also employed.
  
  
  RESULTS
  The results from MTT and trypan blue exclusion assays represented reduction of the cells viability. Extractability of histones and HMG proteins contrasted with difficulty as their content was decreased on SDS-gel upon increasing drug concentration as western blots confirmed it. The amount of degradation form of PARP (89 KD) increased significantly in a dose dependent manner. Increase in anion superoxide production and DNA fragmentation together with cytological detection of chromatin condensation and cellular damage upon exposure of the cells to vinorelbine were indicative of apoptosis induction in these normal cells.
  
  
  CONCLUSIONS
  Vinorelbine is genotoxic in non-adherent bone marrow cells as affects chromatin components, DNA, histone and HMGB1 proteins and induces apoptosis.
authors.affiliation: Department of Biochemistry, Institute of Biochemistry and Biophysics, University of Tehran , Tehran , Iran.
authors.forename: Azra
authors.initials: A
authors.lastname: Rabbani-Chadegani
authors.forename: Parisa
authors.initials: P
authors.lastname: Paydar
authors.forename: Marzieh
authors.initials: M
authors.lastname: Amirshenava
authors.forename: Asieh
authors.initials: A
authors.lastname: Aramvash
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000473:pathology; D002448:Cell Adhesion; D002470:Cell Survival / Q000187:drug effects; D002843:Chromatin / Q000187:drug effects / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D024002:HMGB Proteins / Q000187:drug effects / Q000378:metabolism; D006657:Histones / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D000077235:Vinorelbine
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002843:Chromatin; D024002:HMGB Proteins; D006657:Histones; D014747:Vinblastine; D000077235:Vinorelbine
keywords: Apoptosis; HMG proteins; chromatin; histones; non-adherent bone marrow cells; vinorelbine