Antineoplastic Effects of NF-kappa B Inhibition by DHMEQ (Dehydroxymethylepoxyquinomicin) Alone and in Co-treatment with Radio-and Chemotherapy in Medulloblastoma Cell Lines

Autor(es)

Ramos, Priscila M. M. ^[1] ; Pezuk, Julia A. ^{[1, 2]} ; Castro-Gamero, Angel M. ^{[1, 3]} ; Oliveira, Harley F. ^[4] ; Scrideli, Carlos A. ^[5] ; Umezawa, Kazuo ^[6] ; Tone, Luiz G. ^{[5, 1]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, Ribeirao Preto, SP - Brazil

^[2] Univ Anhaguera Sao Paulo, UNIAN SP, Sao Paulo, SP - Brazil

^[3] Univ Fed Alfenas, Inst Nat Sci, Alfenas, MG - Brazil

^[4] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Clin Med, Ribeirao Preto, SP - Brazil

^[5] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pediat, Ribeirao Preto, SP - Brazil

^[6] Aichi Med Univ, Dept Mol Target Med Screening, Nagakute, Aichi - Japan

• Tipo de documento: Artigo Científico
• Fonte: ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY; v. 18, n. 4, p. 541-549, 2018.
• Citações Web of Science: 3

Resumo

Background: NF-kappa B is a transcription factor involved in the transcriptional regulation of a large number of genes related to tumorigenesis in several cancer cell types, and its inhibition has been related to anticancer effect. DHMEQ (Dehydroxymethylepoxyquinomicin) is a compound that blocks the translocation of NF-kappa B from the cytoplasm to the nucleus, thus inhibiting its activity as a transcriptional activator. Several studies have shown the antineoplastic effects of DHMEQ in numerous tumor types, however, there are no surveys that tested their effects in MB. Objectives: The aim of the present study was to evaluate the effects of DHMEQ as NF-kappa B inhibitor in pediatric MB cell lines. Method: We used the UW402, UW473 and ONS-76 medulloblastoma (MB) cell lines to verify the effect of DHMEQ on proliferation, clonogenic capacity, apoptosis, cell invasion and migration, and evaluated the effect of the combination with other drugs and the potential as a radiosensitizator. Results: A significant decrease in the cell growth, a strong inhibition of the clonogenic capacity, migration and cell invasion was observed after NF-kappa B inhibition in the three MB cell lines. Conversely, increased level of apoptosis rates were demonstrated. Additionally, treatments with DHMEQ combined with other chemotherapeutic agents were synergic in most points, and a strong radiosensitization by this compound was observed in the three MB cell lines. Conclusion: DHMEQ has potential antitumor effect on MB cells, and it may be considered a new therapeutic agent to improve treatment approaches in MB. (AU)

• Processo FAPESP: 10/18792-2 - Avaliação dos efeitos anti-neoplásicos da inibição do NFKB pelo DHMEQ(Dehydroxymethylepoxyquinomicin) em linhagens celulares de meduloblastoma
• Beneficiário: Priscila Maria Manzini Ramos
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 11/01026-8 - POLO-LIKE QUINASES EM MEDULOBLASTOMA: Avaliação da expressão dos genes PLKs e efeitos in vitro da inibição farmacológica da PLK1.
• Beneficiário: Julia Alejandra Pezuk
• Modalidade de apoio: Bolsas no Brasil - Doutorado