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Article

S100B-p53 disengagement by pentamidine promotes apoptosis and inhibits cellular migration via aquaporin-4 and metalloproteinase-2 inhibition in C6 glioma cells

  • Authors:
    • Elena Capoccia
    • Carla Cirillo
    • Annalisa Marchetto
    • Samanta Tiberi
    • Youssef Sawikr
    • Marcella Pesce
    • Alessandra D'Alessandro
    • Caterina Scuderi
    • Giovanni Sarnelli
    • Rosario Cuomo
    • Luca Steardo
    • Giuseppe Esposito
  • View Affiliations / Copyright

    Affiliations: Department of Physiology and Pharmacology ̔Vittorio Erspamer̓, Sapienza University of Rome, Rome I‑00185, Italy, Laboratory for Enteric Neuroscience, Translational Research Center for Gastrointestinal Disorders, University of Leuven, Leuven 3000, Belgium, Department of Clinical and Experimental Medicine, Gastroenterology Unit, University of Naples Federico II, Naples I‑80131, Italy
  • Pages: 2864-2870
    |
    Published online on: April 1, 2015
       https://doi.org/10.3892/ol.2015.3091
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Abstract

S100 calcium-binding protein B (S100B) is highly expressed in glioma cells and promotes cancer cell survival via inhibition of the p53 protein. In melanoma cells, this S100B‑p53 interaction is known to be inhibited by pentamidine isethionate, an antiprotozoal agent. Thus, the aim of the present study was to evaluate the effect of pentamidine on rat C6 glioma cell proliferation, migration and apoptosis in vitro. The change in C6 cell proliferation following treatment with pentamidine was determined by performing a 3‑[4,5‑dimethylthiazol‑2‑yl]‑2,5 diphenyltetrazolium bromide‑formazan assay. Significant dose‑dependent decreases in proliferation were observed at pentamidine concentrations of 0.05 µM (58.5±5%; P<0.05), 0.5 µM (40.6±7%; P<0.01) and 5 µM (13±4%; P<0.001) compared with the control (100% viability). Furthermore, treatment with 0.05, 0.5 and 5 µM pentamidine was associated with a significant increase in apoptosis versus the untreated cells, as determined by DNA fragmentation assays, immunofluorescence analysis of C6 chromatin using Hoechst staining, and immunoblot analysis of B‑cell lymphoma‑2 (Bcl‑2)‑associated X protein (100%, P<0.05; 453%, P<0.01; and 1000%, P<0.001, respectively) and Bcl‑2 (‑60%, P<0.001; ‑80.13%, P<0.001; ‑95%, P<0.001, respectively). In addition, the administration of 0.05, 0.5 and 5 µM pentamidine significantly upregulated the protein expression levels of p53 (681±87.5%, P<0.05; 1244±94.3%, P<0.01; and 2244±111%, P<0.001, respectively), and significantly downregulated the expression levels of matrix metalloproteinase‑2 (42±2.3%, P<0.05; 71±2.5%, P<0.01; and 95.8±3.3%, P<0.001, respectively) and aquaporin 4 (38±2.5%, P<0.05; 69±2.6%, P<0.01; and 88±3.0%, P<0.001, respectively), compared with the untreated cells. The wound healing assay demonstrated that cell migration was significantly impaired by treatment with 0.05, 0.5 and 5 µM pentamidine compared with untreated cells (88±4.2%, P<0.05; 64±2%, P<0.01; and 42±3.1%, P<0.001, respectively). Although additional in vivo studies are required to clarify the current in vitro data, the present study indicates that pentamidine and S100B‑p53 inhibitors may represent a novel approach for the treatment of glioma.
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Copy and paste a formatted citation
Spandidos Publications style
Capoccia E, Cirillo C, Marchetto A, Tiberi S, Sawikr Y, Pesce M, D'Alessandro A, Scuderi C, Sarnelli G, Cuomo R, Cuomo R, et al: S100B-p53 disengagement by pentamidine promotes apoptosis and inhibits cellular migration via aquaporin-4 and metalloproteinase-2 inhibition in C6 glioma cells. Oncol Lett 9: 2864-2870, 2015.
APA
Capoccia, E., Cirillo, C., Marchetto, A., Tiberi, S., Sawikr, Y., Pesce, M. ... Esposito, G. (2015). S100B-p53 disengagement by pentamidine promotes apoptosis and inhibits cellular migration via aquaporin-4 and metalloproteinase-2 inhibition in C6 glioma cells. Oncology Letters, 9, 2864-2870. https://doi.org/10.3892/ol.2015.3091
MLA
Capoccia, E., Cirillo, C., Marchetto, A., Tiberi, S., Sawikr, Y., Pesce, M., D'Alessandro, A., Scuderi, C., Sarnelli, G., Cuomo, R., Steardo, L., Esposito, G."S100B-p53 disengagement by pentamidine promotes apoptosis and inhibits cellular migration via aquaporin-4 and metalloproteinase-2 inhibition in C6 glioma cells". Oncology Letters 9.6 (2015): 2864-2870.
Chicago
Capoccia, E., Cirillo, C., Marchetto, A., Tiberi, S., Sawikr, Y., Pesce, M., D'Alessandro, A., Scuderi, C., Sarnelli, G., Cuomo, R., Steardo, L., Esposito, G."S100B-p53 disengagement by pentamidine promotes apoptosis and inhibits cellular migration via aquaporin-4 and metalloproteinase-2 inhibition in C6 glioma cells". Oncology Letters 9, no. 6 (2015): 2864-2870. https://doi.org/10.3892/ol.2015.3091
Copy and paste a formatted citation
x
Spandidos Publications style
Capoccia E, Cirillo C, Marchetto A, Tiberi S, Sawikr Y, Pesce M, D'Alessandro A, Scuderi C, Sarnelli G, Cuomo R, Cuomo R, et al: S100B-p53 disengagement by pentamidine promotes apoptosis and inhibits cellular migration via aquaporin-4 and metalloproteinase-2 inhibition in C6 glioma cells. Oncol Lett 9: 2864-2870, 2015.
APA
Capoccia, E., Cirillo, C., Marchetto, A., Tiberi, S., Sawikr, Y., Pesce, M. ... Esposito, G. (2015). S100B-p53 disengagement by pentamidine promotes apoptosis and inhibits cellular migration via aquaporin-4 and metalloproteinase-2 inhibition in C6 glioma cells. Oncology Letters, 9, 2864-2870. https://doi.org/10.3892/ol.2015.3091
MLA
Capoccia, E., Cirillo, C., Marchetto, A., Tiberi, S., Sawikr, Y., Pesce, M., D'Alessandro, A., Scuderi, C., Sarnelli, G., Cuomo, R., Steardo, L., Esposito, G."S100B-p53 disengagement by pentamidine promotes apoptosis and inhibits cellular migration via aquaporin-4 and metalloproteinase-2 inhibition in C6 glioma cells". Oncology Letters 9.6 (2015): 2864-2870.
Chicago
Capoccia, E., Cirillo, C., Marchetto, A., Tiberi, S., Sawikr, Y., Pesce, M., D'Alessandro, A., Scuderi, C., Sarnelli, G., Cuomo, R., Steardo, L., Esposito, G."S100B-p53 disengagement by pentamidine promotes apoptosis and inhibits cellular migration via aquaporin-4 and metalloproteinase-2 inhibition in C6 glioma cells". Oncology Letters 9, no. 6 (2015): 2864-2870. https://doi.org/10.3892/ol.2015.3091
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