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NF-кB inhibition by DHMEQ: in vitro antiproliferative effects on pilocytic astrocytoma and concise review of the current literature

Child's Nervous System volume 36, pages 2675–2684 (2020)Cite this article

Abstract

Introduction

Pilocytic astrocytoma (PA) is the most common brain tumor that affects the pediatric population. Even though PA is benign and treatment only involves surgery, recurrent or unresectable tumors require chemo- and radiotherapy. Besides BRAF, CDKN2A, or IDH mutations, the hyperactivation of the nuclear factor NF-κB contributes to tumor growth and survival.

Methods

In the present study, we used publicly available data for the in silico analysis of NF-κB subunits (RELA, RELB, REL, NF-κB1, and NF-κB2) expression in PA samples. Besides, in vitro assays were performed to evaluate proliferation, migration, cell death, on the PA cell line Res286 comparing to human primary astrocytes. Sensitization to radiation therapy and temozolomide (TMZ) was also assayed.

Results

Our results showed that all the members of the NF-kB family are upregulated in PA datasets compared to normal brain tissues. Moreover, DHMEQ treatment significantly reduced cell growth and motility, while sensitized cells to ionizing radiation and TMZ, as previously seen in high-grade gliomas.

Conclusions

This drug presents a potential application in clinical practice for the treatment of recurrent or inoperable PA. Moreover, its use might assist adjuvant chemotherapy and reduce irradiation doses to avoid toxicity to the surrounding tissues.

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Funding

This research was supported by the Young Investigators Program (2010/50635-4 and 2010/16652-9 to M.S.B) from FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo), Brazil.

Author information

Affiliations

  1. Department of Cell and Molecular Biology, Ribeirão Preto Medical School, University of São Paulo, Ribeirao Preto, São Paulo, Brazil

    M. F. Candido & M. Medeiros

  2. Regional Blood Center of Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo, Ribeirao Preto, São Paulo, Brazil

    G. C. Baldissera

  3. Department of Molecular Target Medicine, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan

    K. Umezawa

  4. Departamento de Biologia, FFCLRP-USP, Av. Bandeirantes, 3900, Bairro Monte Alegre, Ribeirao Preto, SP, CEP 14040-901, Brazil

    María Sol Brassesco

Authors
  1. M. F. Candido
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  2. G. C. Baldissera
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  3. M. Medeiros
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  4. K. Umezawa
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  5. María Sol Brassesco
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Correspondence to María Sol Brassesco.

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Candido, M.F., Baldissera, G.C., Medeiros, M. et al. NF-кB inhibition by DHMEQ: in vitro antiproliferative effects on pilocytic astrocytoma and concise review of the current literature. Childs Nerv Syst 36, 2675–2684 (2020). https://doi.org/10.1007/s00381-020-04625-3

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Keywords

  • Low-grade glioma
  • Inoperable tumor
  • Dehydroxymethylepoxyquinomicin
  • Adjuvant chemotherapy