title: Ascorbic acid induces either differentiation or apoptosis in MG-63 osteosarcoma lineage.
abstract: OBJECTIVE
  Osteosarcoma originates from mesenchymal stem cells with impaired bone differentiation. In the present study we investigated the effect of ascorbic acid (AsA) on osteogenic differentiation and apoptosis of the MG-63 osteosarcoma cell line.
  
  
  METHODS
  We evaluated the expression of runt-related transcription factor-2 (RUNX2) and secreted phosphoprotein 1 (SPP1) genes by real-time Polymerase Chain Reaction (PCR) and of endogenous bone morphogenetic protein-2 (BMP2) and osteocalcin proteins by immunohistochemistry. We analyzed osteoblast maturation by phosphatase alkaline synthesis and calcium deposition, and apoptosis by (TUNEL) test and Annexin staining.
  
  
  RESULTS
  Our results showed that RUNX2 and SPP1 gene expression was increased in cells treated with low concentrations of AsA with respect to untreated cells. At higher concentrations, AsA induced apoptosis of osteosarcoma cells, possibly with the involvement of p21.
  
  
  CONCLUSIONS
  Our findings support the ability of AsA to induce both differentiation, by affecting the target involved in early and late phases of osteogenic maturation, and apoptosis in poorly-differentiated osteosarcoma cells.
authors.affiliation: Department of Medicine, Clinic of Internal Medicine, section D, University of Verona, Piazzale Scuro, 10, 37134 Verona, Italy. luca.dallecarbonare@univr.it.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Valenti
authors.forename: Mirko
authors.initials: M
authors.lastname: Zanatta
authors.forename: Luca
authors.initials: L
authors.lastname: Donatelli
authors.forename: Gianmaria
authors.initials: G
authors.lastname: Viviano
authors.forename: Chiara
authors.initials: C
authors.lastname: Cavallini
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Scupoli
authors.forename: Luca
authors.initials: L
authors.lastname: Dalle Carbonare
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001205:Ascorbic Acid / Q000494:pharmacology*; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D019070:Cell Lineage / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D055396:Bone Morphogenetic Protein 2; D050659:Core Binding Factor Alpha 1 Subunit; C506895:SPP1 protein, human; D053495:Osteopontin; D001205:Ascorbic Acid
keywords: Ascorbic acid; apopotosis; differentiation; osteoblast; osteosarcoma