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

Author(s)

Candido, M. F. ^[1] ; Baldissera, G. C. ^[2] ; Medeiros, M. ^[1] ; Umezawa, K. ^[3] ; Brassesco, Maria Sol ^[4]

Affiliation

^[1] Univ Sao Paulo, Dept Cell & Mol Biol, Ribeirao Preto Med Sch, Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Reg Blood Ctr Ribeirao Preto, Ribeirao Preto Med Sch, Ribeirao Preto, SP - Brazil

^[3] Aichi Med Univ, Dept Mol Target Med, Sch Med, Nagakute, Aichi - Japan

^[4] FFCLRP USP, Dept Biol, Ave Bandeirantes 3900, BR-14040901 Ribeirao Preto, SP - Brazil

• Document type: Review article
• Source: CHILD'S NERVOUS SYSTEM; v. 36, n. 11 MAY 2020.
• Web of Science Citations: 0

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-kappa B contributes to tumor growth and survival. Methods In the present study, we used publicly available data for the in silico analysis of NF-kappa B subunits (RELA, RELB, REL, NF-kappa B1, and NF-kappa B2) 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. (AU)

• FAPESP's process: 10/16652-9 - NF-kB inhibition in glioblastoma: in vitro and in vivo effects of DHMEQ in tumor chemoresistance, invasion and progression
• Grantee: María Sol Brassesco Annichini
• Support Opportunities: Scholarships in Brazil - Young Researchers
• FAPESP's process: 10/50635-4 - NF-Kb inhibition in glioblastoma: in vitro and in vivo effects of DHMEQ in tumor chemoresistence, invasion and progression
• Grantee: María Sol Brassesco Annichini
• Support Opportunities: Research Grants - Young Investigators Grants