title: Analysis of proliferation and apoptotic induction by 20 steroid glycosides in 143B osteosarcoma cells in vitro.
abstract: OBJECTIVE
  Osteosarcoma is the most common type of malignant bone tumour in children and adolescents; it has poor prognosis, is highly metastatic and is resistant to current therapeutic approaches. In this study, different herbal extracts used in phytotherapy have been screened after searching innovative natural anti-cancer components.
  
  
  METHODS
  Twenty steroid glycosides were examined for accordance to their potential of inhibiting cell proliferation and inducing apoptosis in the osteosarcoma cell line 143B. Cell proliferation was examined using a CASY counter. Effects of cardiac glycosides on induction of apoptosis were evaluated by Annexin V-APC and flow cytometry, caspase activity assay and measurement of mitochondrial membrane potential.
  
  
  RESULTS
  The study revealed that various steroid glycosides suppress cell proliferation in a concentration-dependent manner. Further investigations indicated apoptotic induction by 17 of the 20 tested cardenolides and bufadienolides. Bufadienolide proscillaridin A, arenobufagin, and cardenolides evomonoside, convallatoxol and ouabain waged strongest apoptotic induction, associated with breakdown of mitochondrial membrane potential and activation of caspases -8 and -9. In contrast, the bufadienolide resibufogenin and cardenolide uzarin had no effect on proliferation inhibition, apoptotic induction or change in mitochondrial membrane potential.
  
  
  CONCLUSIONS
  These results indicate that bufadienolides proscillaridin A and arenobufagin and cardenolide evomonoside, or related natural compounds might be promising new starting points for development of novel anti-cancer agents for treatment of osteosarcoma.
authors: Department of Paediatric Oncology/Haematology, Otto-Heubner-Centre for Paediatric and Adolescent Medicine (OHC), Charité, Universitaetsmedizin Berlin, Berlin, 13353, Germany.
authors: C I
authors: CI
authors: Delebinski
authors: FU Berlin, Institute for Pharmacy, Berlin, 14195, Germany.
authors: S
authors: S
authors: Georgi
authors: Department of Paediatric Oncology/Haematology, Otto-Heubner-Centre for Paediatric and Adolescent Medicine (OHC), Charité, Universitaetsmedizin Berlin, Berlin, 13353, Germany.
authors: S
authors: S
authors: Kleinsimon
authors: Department of Paediatric Oncology/Haematology, Otto-Heubner-Centre for Paediatric and Adolescent Medicine (OHC), Charité, Universitaetsmedizin Berlin, Berlin, 13353, Germany.
authors: M
authors: M
authors: Twardziok
authors: Department of Pharmacognosy, University of Vienna, Vienna, A-1090, Austria.
authors: B
authors: B
authors: Kopp
authors: FU Berlin, Institute for Pharmacy, Berlin, 14195, Germany.
authors: M F
authors: MF
authors: Melzig
authors: Department of Paediatric Oncology/Haematology, Otto-Heubner-Centre for Paediatric and Adolescent Medicine (OHC), Charité, Universitaetsmedizin Berlin, Berlin, 13353, Germany.
authors: G
authors: G
authors: Seifert
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D006027:Glycosides / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology; D013256:Steroids / Q000737:chemistry
chemical_list: D006027:Glycosides; D013256:Steroids; D053181:Caspase 8; D053453:Caspase 9