In vitro antitumor effect of sodium butyrate and zoledronic acid combined with traditional chemotherapeutic drugs: a paradigm of synergistic molecular targeting in the treatment of Ewing sarcoma

  • Authors:
    • Michel Pinheiro Dos Santos
    • Caroline Brunetto de Farias
    • Rafael Roesler
    • Algemir Lunardi Brunetto
    • Ana Lucia Abujamra
  • View Affiliations

  • Published online on: December 6, 2013     https://doi.org/10.3892/or.2013.2907
  • Pages: 955-968
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Abstract

Histone deacetylase inhibitors and bisphosphonates have a promising future in the treatment of cancer as targeted anticancer drugs, particularly when used together or in combination with other cytotoxic agents. However, the effects of these combined treatments have not yet been systematically evaluated in Ewing sarcoma. The in vitro effects on cellular proliferation, viability and survival were investigated in two Ewing sarcoma cell lines, SK-ES-1 and RD-ES. The cell lines were treated with sodium butyrate, a histone deacetylase inhibitor and zoledronic acid, a bisphosphonate, alone, together or in combination with chemotherapeutic drugs recommended for clinical treatment of Ewing sarcoma. The data demonstrated that the combination of sodium butyrate and zoledronic acid had a synergistic cytotoxic effect at 72 h following treatment, persisting for 10-14 days post-treatment, in both cell lines tested. All combinations between sodium butyrate or zoledronic acid and the traditional antineoplastic drugs (doxorubicin, etoposide and vincristine) demonstrated a synergistic cytotoxic effect at 72 h in SK-ES-1 and RD-ES cells, except for the combinations of sodium butyrate with vincristine and of zoledronic acid with doxorubicin, which showed only an additive effect in RD-ES cell lines as compared to each agent alone. These acute effects observed in both Ewing sarcoma cell lines were confirmed by the clonogenic assay. The present data suggest that combining histone deacetylase inhibitors and bisphosphonates with traditional chemotherapeutic drugs is a promising therapeutic strategy for the treatment of Ewing sarcoma, and provides a basis for further studies in this field.

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2014-February
Volume 31 Issue 2

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Dos Santos MP, de Farias CB, Roesler R, Brunetto AL and Abujamra AL: In vitro antitumor effect of sodium butyrate and zoledronic acid combined with traditional chemotherapeutic drugs: a paradigm of synergistic molecular targeting in the treatment of Ewing sarcoma. Oncol Rep 31: 955-968, 2014
APA
Dos Santos, M.P., de Farias, C.B., Roesler, R., Brunetto, A.L., & Abujamra, A.L. (2014). In vitro antitumor effect of sodium butyrate and zoledronic acid combined with traditional chemotherapeutic drugs: a paradigm of synergistic molecular targeting in the treatment of Ewing sarcoma. Oncology Reports, 31, 955-968. https://doi.org/10.3892/or.2013.2907
MLA
Dos Santos, M. P., de Farias, C. B., Roesler, R., Brunetto, A. L., Abujamra, A. L."In vitro antitumor effect of sodium butyrate and zoledronic acid combined with traditional chemotherapeutic drugs: a paradigm of synergistic molecular targeting in the treatment of Ewing sarcoma". Oncology Reports 31.2 (2014): 955-968.
Chicago
Dos Santos, M. P., de Farias, C. B., Roesler, R., Brunetto, A. L., Abujamra, A. L."In vitro antitumor effect of sodium butyrate and zoledronic acid combined with traditional chemotherapeutic drugs: a paradigm of synergistic molecular targeting in the treatment of Ewing sarcoma". Oncology Reports 31, no. 2 (2014): 955-968. https://doi.org/10.3892/or.2013.2907