Title:Antineoplastic Effects of NF-κB Inhibition by DHMEQ (Dehydroxymethylepoxyquinomicin) Alone and in Co-treatment with Radio-and Chemotherapy in Medulloblastoma Cell Lines
VOLUME: 18 ISSUE: 4
Author(s):Priscila M.M. Ramos*, Julia A. Pezuk, Angel M. Castro-Gamero, Harley F. Oliveira, Carlos A. Scrideli, Kazuo Umezawa and Luiz G. Tone
Affiliation:Department of Genetics, Ribeirao Preto Medical School, University of Sao Paulo, Department of Genetics, Ribeirao Preto Medical School, University of Sao Paulo, Department of Genetics, Ribeirao Preto Medical School, University of Sao Paulo, Department of Clinical Medical, Ribeirao Preto Medical School, University of Sao Paulo, Department of Pediatric, Ribeirao Preto Medical School, University of Sao Paulo, Department of Molecular Target Medicine Screening, Aichi Medical University. Nagakute, Aichi, Department of Genetics, Ribeirao Preto Medical School, University of Sao Paulo
Keywords:DHMEQ, NFκB, medulloblastoma, molecular target, chemotherapy, cell lines.
Abstract:Background: NF-κB 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-κB 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-κB 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-κB 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.
