Betulinic Acid Derivatives NVX-207 and B10 for Treatment of Glioblastoma—An in Vitro Study of Cytotoxicity and Radiosensitization

International Journal of Molecular Sciences

Matthias Bache¹  Stephan Bernhardt¹  Sarina Passin¹  Henri Wichmann¹  Anja Hein¹  Martin Zschornak¹  Matthias Kappler⁴  Helge Taubert²  Reinhard Paschke³  Dirk Vordermark¹ 

[1]Department of Radiotherapy, Martin Luther University Halle–Wittenberg, Ernst Grube Straße 40, D-06120 Halle, Germany

[2] E-Mails:

[3]Clinic of Urology, Friedrich Alexander University Hospital Erlangen, Hartmann Str. 14, D-91054 Erlangen, Germany

[4] E-Mail:

[5]Biozentrum, Martin Luther Universität Halle–Wittenberg, Weinbergweg 22, D-06120 Halle, Germany

[6] E-Mail:

[7]Department of Oral and Maxillofacial Plastic Surgery, Martin Luther University Halle–Wittenberg, Ernst Grube Straße 40, D-06120 Halle, Germany

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关键词: betulinic acid derivatives;    glioma;    cytotoxicity;    irradiation;    normoxia;    hypoxia;   

DOI  :  10.3390/ijms151119777

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.