Induction of differentiation and suppression of malignant phenotype of human neuroblastoma BE(2)-C cells by valproic acid: Enhancement by combination with interferon-α

  • Authors:
    • Jindrich Cinatl
    • R. Kotchetkov
    • R. Blaheta
    • P. H. Driever
    • J.-U. Vogel
    • Jaroslav Cinatl
  • View Affiliations

  • Published online on: January 1, 2002     https://doi.org/10.3892/ijo.20.1.97
  • Pages: 97-106
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Abstract

Valproic acid (VPA) has been shown to induce growth-arrest and differentiation of human neuroectodermal tumors similarly to several other fatty acids. In the present study, we show that continuous VPA treatment together with Interferon-α (INF-α) synergistically inhibited cell growth of a well-established model of neuroblastoma (NB) differentiation using the human N-myc amplified cell line BE(2)-C. Suppression of tumor growth was accompanied by morphological features of neuronal differentiation and inhibition of histone deacetylase activity. Furthermore, induction of differentiation was concomitant with altered expression of genes related to malignant phenotype such as down-regulation of N-myc, induction of bcl-2 and neural cell adhesion molecule. Production of inhibitors of angiogenesis like thrombospondin-1 and activin A was up-regulated in differentiated NB cells. Treatment with VPA alone decreased the ability of BE(2)-C cells to adhere to and penetrate human endothelium. All these effects of VPA were significantly enhanced when combined with INF-α which on its own had little or no effect. These results suggest that combination of VPA and INF-α may provide a novel therapeutic strategy for NB due to enhanced inhibition of tumor cell growth, induction of tumor differentiation and suppression of malignant biology by reduced angiogenic and decreased metastatic potentials.

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January 2002
Volume 20 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Cinatl, J., Kotchetkov, R., Blaheta, R., Driever, P.H., Vogel, J., & Cinatl, J. (2002). Induction of differentiation and suppression of malignant phenotype of human neuroblastoma BE(2)-C cells by valproic acid: Enhancement by combination with interferon-α. International Journal of Oncology, 20, 97-106. https://doi.org/10.3892/ijo.20.1.97
MLA
Cinatl, J., Kotchetkov, R., Blaheta, R., Driever, P. H., Vogel, J., Cinatl, J."Induction of differentiation and suppression of malignant phenotype of human neuroblastoma BE(2)-C cells by valproic acid: Enhancement by combination with interferon-α". International Journal of Oncology 20.1 (2002): 97-106.
Chicago
Cinatl, J., Kotchetkov, R., Blaheta, R., Driever, P. H., Vogel, J., Cinatl, J."Induction of differentiation and suppression of malignant phenotype of human neuroblastoma BE(2)-C cells by valproic acid: Enhancement by combination with interferon-α". International Journal of Oncology 20, no. 1 (2002): 97-106. https://doi.org/10.3892/ijo.20.1.97