title: Inhibition of human glioma cell proliferation by altered Bax/Bcl-2-p53 expression and apoptosis induction by Rhaponticum carthamoides extracts from transformed and normal roots.
abstract: OBJECTIVE
  The objective of this study was to determine the cytotoxic effect and apoptotic activity of Rhaponticum carthamoides transformed root (TR) and root of soil-grown plant (NR) extracts in a human glioma primary cells. The effect of these root extracts on cell cycle arrest, mitochondrial membrane potential (ΔΨm) and expression levels of apoptosis-related genes (Bcl-2, Bax and p53) were also examined.
  
  
  METHODS
  Cytotoxic activity of root extracts was evaluated by MTT assay. Apoptosis and cell cycle were determined by flow cytometry. Expression levels of apoptosis-related gene were analysed by RT-PCR and Western blotting. ΔΨm was examined by the use of JC-1 reagent.
  
  
  RESULTS
  Rhaponticum carthamoides root extracts inhibit cell growth and induce apoptosis in a dose-dependent manner in human glioma cells. The root extracts were found to up-regulate the pro-apoptotic Bax protein and down-regulate the anti-apoptotic Bcl-2 protein, consequently increasing the ratios of Bax/Bcl-2 protein levels. Moreover, an increase of the p53 protein level and reduction of ΔΨm in glioma cells were observed after treatment with NR and TR extracts.
  
  
  CONCLUSIONS
  The results of this study may offer a new insight into the potential anticancer activity of R. carthamoides root extracts.
authors.affiliation: Department of Biology and Pharmaceutical Botany, Medical University of Łódź, Poland. ewa.skala@umed.lodz.pl.
authors.forename: Ewa
authors.initials: E
authors.lastname: Skała
authors.affiliation: Department of Biology and Pharmaceutical Botany, Medical University of Łódź, Poland.
authors.forename: Przemysław
authors.initials: P
authors.lastname: Sitarek
authors.affiliation: Department of Molecular Genetics, University of Łódź, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Toma
authors.affiliation: Department of Medical Biochemistry, Medical University of Łódź, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Szemraj
authors.affiliation: Department of Neurosurgery and Peripheral Nerve Surgery, Medical University of Łódź, University Hospital WAM-CSW, Łódź, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Radek
authors.affiliation: Department of Microbiology and Immunology, Fels Institute for Cancer Research and Molecular Biology, Temple University, School of Medicine, Philadelphia, PA, USA.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Nieborowska-Skorska
authors.affiliation: Department of Microbiology and Immunology, Fels Institute for Cancer Research and Molecular Biology, Temple University, School of Medicine, Philadelphia, PA, USA.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Skorski
authors.affiliation: Department of Biology and Pharmaceutical Botany, Medical University of Łódź, Poland.
authors.forename: Halina
authors.initials: H
authors.lastname: Wysokińska
authors.affiliation: Department of Molecular Genetics, University of Łódź, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Śliwiński
mesh_terms: D060054:Agrobacterium / Q000502:physiology; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005910:Glioma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D043843:Leuzea / Q000737:chemistry* / Q000382:microbiology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008856:Microscopy, Fluorescence; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry* / Q000382:microbiology; D010946:Plants, Medicinal; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D014169:Transformation, Bacterial; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C494826:BAX protein, human; C000595707:BCL2 protein, human; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein
keywords: 
  Bax
  ; 
  Rhaponticum carthamoides
  ; Bcl-2 and p53 gene expressions; apoptosis; caffeic acid derivatives; glioma primary cells; mitochondrial membrane potential