title: Betulinic acid derivatives NVX-207 and B10 for treatment of glioblastoma--an in vitro study of cytotoxicity and radiosensitization.
abstract: Betulinic acid (BA), a pentacyclic triterpene, represents a new therapeutic substance that has potential benefits for treating glioblastoma. Recently, new strategies for producing BA derivatives with improved properties have evolved. However, few studies have examined the combination of BA or BA derivatives using radiotherapy. The effects of two BA derivatives, NVX-207 and B10, on cellular and radiobiological behavior were analyzed using glioblastoma cell lines (U251MG, U343MG and LN229). Based on IC50 values under normoxic conditions, we detected a 1.3-2.9-fold higher cytotoxicity of the BA derivatives B10 and NVX-207, respectively, compared to BA. Incubation using both BA derivatives led to decreased cell migration, cleavage of PARP and decreased protein expression levels of Survivin. Weak radiation sensitivity enhancement was observed in U251MG cells after treatment with both BA derivatives. The enhancement factors at an irradiation dose of 6 Gy after treatment with 5 µM NVX-207 and 5 µM B10 were 1.32 (p=0.029) and 1.55 (p=0.002), respectively. In contrast to BA, neither NVX-207 nor B10 had additional effects under hypoxic conditions. Our results suggest that the BA derivatives NVX-207 and B10 improve the effects of radiotherapy on human malignant glioma cells, particularly under normoxic conditions.
authors.affiliation: Department of Radiotherapy, Martin Luther University Halle-Wittenberg, Ernst Grube Straße 40, D-06120 Halle, Germany. matthias.bache@medizin.uni-halle.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Bache
authors.affiliation: Department of Radiotherapy, Martin Luther University Halle-Wittenberg, Ernst Grube Straße 40, D-06120 Halle, Germany. s.bernhardt@dkfz-heidelberg.de.
authors.forename: Stephan
authors.initials: S
authors.lastname: Bernhardt
authors.affiliation: Department of Radiotherapy, Martin Luther University Halle-Wittenberg, Ernst Grube Straße 40, D-06120 Halle, Germany. Sarina.Passin@web.de.
authors.forename: Sarina
authors.initials: S
authors.lastname: Passin
authors.affiliation: Department of Radiotherapy, Martin Luther University Halle-Wittenberg, Ernst Grube Straße 40, D-06120 Halle, Germany. wichmann.henri@medizin.uni-halle.de.
authors.forename: Henri
authors.initials: H
authors.lastname: Wichmann
authors.affiliation: Department of Radiotherapy, Martin Luther University Halle-Wittenberg, Ernst Grube Straße 40, D-06120 Halle, Germany. anjahn@hein-reica.de.
authors.forename: Anja
authors.initials: A
authors.lastname: Hein
authors.affiliation: Department of Radiotherapy, Martin Luther University Halle-Wittenberg, Ernst Grube Straße 40, D-06120 Halle, Germany. mc_scop@gmx.net.
authors.forename: Martin
authors.initials: M
authors.lastname: Zschornak
authors.affiliation: Department of Oral and Maxillofacial Plastic Surgery, Martin Luther University Halle-Wittenberg, Ernst Grube Straße 40, D-06120 Halle, Germany. matthias.kappler@medizin.uni-halle.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Kappler
authors.affiliation: Clinic of Urology, Friedrich Alexander University Hospital Erlangen, Hartmann Str. 14, D-91054 Erlangen, Germany. Helge.Taubert@uk-erlangen.de.
authors.forename: Helge
authors.initials: H
authors.lastname: Taubert
authors.affiliation: Biozentrum, Martin Luther Universität Halle-Wittenberg, Weinbergweg 22, D-06120 Halle, Germany. reinhard.paschke@biozentrum.uni-halle.de.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Paschke
authors.affiliation: Department of Radiotherapy, Martin Luther University Halle-Wittenberg, Ernst Grube Straße 40, D-06120 Halle, Germany. dirk.vordermark@medizin.uni-halle.de.
authors.forename: Dirk
authors.initials: D
authors.lastname: Vordermark
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects* / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology; D005960:Glucosides / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D053978:Pentacyclic Triterpenes; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011412:Propanolamines / Q000737:chemistry / Q000494:pharmacology*; D011839:Radiation, Ionizing; D000077022:Survivin; D014315:Triterpenes / Q000737:chemistry* / Q000494:pharmacology*; D000094062:Betulinic Acid
chemical_list: C000599178:2-amino-3-hydroxy-2-hydroxymethylpropyl 3-acetylbetulinoate; C000599179:28-O-acetylbetulin-3-ylglucopyranoside; D000972:Antineoplastic Agents, Phytogenic; C107489:BIRC5 protein, human; D005960:Glucosides; D051034:Inhibitor of Apoptosis Proteins; D053978:Pentacyclic Triterpenes; D011412:Propanolamines; D000077022:Survivin; D014315:Triterpenes; D011065:Poly(ADP-ribose) Polymerases; D000094062:Betulinic Acid