Aberrantly expressed microRNAs and their implications in childhood central nervous system tumors.

Even though the treatment of childhood cancer has evolved significantly in recent decades, aggressive central nervous system (CNS) tumors are still a leading cause of morbidity and mortality in this population. Consequently, the identification of molecular targets that can be incorporated into diagnostic practice, effectively predict prognosis, follow treatment response, and materialize into potential targeted therapeutic approaches are still warranted. Since the first evidence of the participation of miRNAs in cancer development and progression 20 years ago, notable progress has been made in the basic understanding of the contribution of their dysregulation as epigenetic driver of tumorigenesis. Nevertheless, among the plethora of articles in the literature, microRNA profiling of pediatric tumors are scarce. This article gives an overview of the recent advances in the diagnostic/prognostic potential of miRNAs in a selection of pediatric CNS tumors: medulloblastoma, ependymoma, pilocytic astrocytoma, glioblastoma, diffuse intrinsic pontine glioma, atypical teratoid/rhabdoid tumors, and choroid plexus tumors.

MicroRNA dysregulation interplay with childhood abdominal tumors.

Abdominal tumors (AT) in children account for approximately 17% of all pediatric solid tumor cases, and frequently exhibit embryonal histological features that differentiate them from adult cancers. Current molecular approaches have greatly improved the understanding of the distinctive pathology of each tumor type and enabled the characterization of novel tumor biomarkers. As seen in abdominal adult tumors, microRNAs (miRNAs) have been increasingly implicated in either the initiation or progression of childhood cancer. Moreover, besides predicting patient prognosis, they represent valuable diagnostic tools that may also assist the surveillance of tumor behavior and treatment response, as well as the identification of the primary metastatic sites. Thus, the present study was undertaken to compile up-to-date information regarding the role of dysregulated miRNAs in the most common histological variants of AT, including neuroblastoma, nephroblastoma, hepatoblastoma, hepatocarcinoma, and adrenal tumors. Additionally, the clinical implications of dysregulated miRNAs as potential diagnostic tools or indicators of prognosis were evaluated.

Should we keep rocking? Portraits from targeting Rho kinases in cancer.

Cancer targeted therapy, either alone or in combination with conventional chemotherapy, could allow the survival of patients with neoplasms currently considered incurable. In recent years, the dysregulation of the Rho-associated coiled-coil kinases (ROCK1 and ROCK2) has been associated with increased metastasis and poorer patient survival in several tumor types, and due to their essential roles in regulating the cytoskeleton, have gained popularity and progressively been researched as targets for the development of novel anti-cancer drugs. Nevertheless, in a pediatric scenario, the influence of both isoforms on prognosis remains a controversial issue. In this review, we summarize the functions of ROCKs, compile their roles in human cancer and their value as prognostic factors in both, adult and pediatric cancer. Moreover, we provide the up-to-date advances on their pharmacological inhibition in pre-clinical models and clinical trials. Alternatively, we highlight and discuss detrimental effects of ROCK inhibition provoked not only by the action on off-targets, but most importantly, by pro-survival effects on cancer stem cells, dormant cells, and circulating tumor cells, along with cell-context or microenvironment-dependent contradictory responses. Together these drawbacks represent a risk for cancer cell dissemination and metastasis after anti-ROCK intervention, a caveat that should concern scientists and clinicians.

MiRNA Dysregulation in Childhood Hematological Cancer.

For decades, cancer biology focused largely on the protein-encoding genes that have clear roles in tumor development or progression: cell-cycle control, apoptotic evasion, genome instability, drug resistance, or signaling pathways that stimulate growth, angiogenesis, or metastasis. MicroRNAs (miRNAs), however, represent one of the more abundant classes of cell modulators in multicellular organisms and largely contribute to regulating gene expression. Many of the ~2500 miRNAs discovered to date in humans regulate vital biological processes, and their aberrant expression results in pathological and malignant outcomes. In this review, we highlight what has been learned about the roles of miRNAs in some of the most common human pediatric leukemias and lymphomas, along with their value as diagnostic/prognostic factors.

PLK1-associated microRNAs are correlated with pediatric medulloblastoma prognosis.

PURPOSE: Medulloblastoma (MB) is the most common malignant tumor of the central nervous system (CNS) in children. Despite its relative good survival rates, treatment can cause long time sequels and may impair patients' lifespan and quality, making the search for new treatment options still necessary. Polo like kinases (PLKs) constitute a five-member serine/threonine kinases family (PLK 1-5) that regulates different stages during cell cycle. Abnormal PLKs expression has been observed in several cancer types, including MB. As gene regulators, miRNAs have also been described with variable expression in cancer. METHODS: We evaluated gene expression profiles of all PLK family members and related miRNAs (miR-100, miR-126, miR-219, and miR-593*) in MB cell lines and tumor samples. RESULTS: RT-qPCR analysis revealed increased levels of PLK1-4 in all cell lines and in most MB samples, while PLK5 was found underexpressed. In parallel, miR-100 was also found upregulated while miR-129, miR-216, and miR-593* were decreased in MB cell lines. Variable miRNAs expression patterns were observed in MB samples. However, a correlation between miR-100 and PLK4 expression was observed, and associations between miR-100, miR-126, and miR-219 expression and overall and event free survival were also evinced in our cohort. Moreover, despite the lack of association with clinico-pathological features, when comparing primary tumors to those relapsed, we found a consistent decrease on PLK2, miR-219, and miR-598* and an increase on miR-100 and miR-126. CONCLUSION: Specific dysregulation on PLKs and associated miRNAs may be important in MB and can be used to predict prognosis. Although miRNAs sequences are fundamental to predict its target, the cell type may also be consider once that mRNA repertoire can define different roles for specific miRNA in a given cell.

BI 6727 and GSK461364 suppress growth and radiosensitize osteosarcoma cells, but show limited cytotoxic effects when combined with conventional treatments.

Polo-like kinase 1 (PLK1), a key regulator of mitosis, is often overexpressed in childhood cancers and is associated with poor prognosis. Previous reports have shown that inhibition of PLK1 might serve as a promising anticancer treatment for osteosarcoma. In this study, we tested the second-generation PLK1 inhibitors BI 6727 and GSK461364 in HOS and MG-63 cell lines, both as a single agent and in combination with methotrexate, cisplatin, vinblastine, doxorubicin, or ionizing radiation. Both PLK1 inhibitors worked equally in terms of cell growth arrest, apoptosis induction, and radiosensitization. Combining BI 6727 or GSK461364 with conventional treatments, however, showed trivial synergistic antitumor effects in vitro. Our results reinforce the potential use of PLK1 inhibitors for a pharmacologic intervention in osteosarcoma, although their applicability in polychemotherapeutic regimens deserves further investigation.

Anticancer activity of 7-epiclusianone, a benzophenone from Garcinia brasiliensis, in glioblastoma.

BACKGROUND: Glioblastoma is the most common tumor of the central nervous system and one of the hardest tumors to treat. Consequently, the search for novel therapeutic options is imperative. 7-epiclusianone, a tetraprenylated benzophenone isolated from the epicarp of the native plant Garcinia brasiliensis, exhibits a range of biological activities but its prospect anticancer activity is underexplored. Thus, the aim of the present study was to evaluate the influence of 7-epiclusianone on proliferation, clonogenic capacity, cell cycle progression and induction of apoptosis in two glioblastoma cell lines (U251MG and U138MG). METHODS: Cell viability was measured by the MTS assay; for the clonogenic assay, colonies were stained with Giemsa and counted by direct visual inspection; For cell cycle analysis, cells were stained with propidium iodide and analyzed by cytometry; Cyclin A expression was determined by immunoblotting; Apoptotic cell death was determined by annexin V fluorescein isothiocyanate labeling and Caspase-3 activity in living cells. RESULTS: Viability of both cell lines was drastically inhibited; moreover, the colony formation capacity was significantly reduced, demonstrating long-term effects even after removal of the drug. 7-epiclusianone treatment at low concentrations also altered cell cycle progression, decreased the S and G2/M populations and at higher concentrations increased the number of cells at sub-G1, in concordance with the increase of apoptotic cells. CONCLUSION: The present study demonstrates for the first time the anticancer potential of 7-epiclusianone against glioblastoma cells, thus meriting its further investigation as a potential therapeutic agent.

BUB1 and BUBR1 inhibition decreases proliferation and colony formation, and enhances radiation sensitivity in pediatric glioblastoma cells.

PURPOSE: Glioblastoma (GBM) is a very aggressive and lethal brain tumor with poor prognosis. Despite new treatment strategies, patients' median survival is still lower than 1 year in most cases. The expression of the BUB gene family has demonstrated to be altered in a variety of solid tumors, pointing to a role as putative therapeutic target. The purpose of this study was to determine BUB1, BUB3, and BUBR1 gene expression profiles in glioblastoma and to analyze the effects of BUB1 and BUBR1 inhibition combined or not with Temozolomide and radiation in the pediatric SF188 GBM cell line. METHODS: For gene expression analysis, 8 cell lines and 18 tumor samples were used. The effect of BUB1 and BUBR1 inhibition was evaluated using siRNA. Apoptosis, cell proliferation, cell cycle kinetics, micronuclei formation, and clonogenic capacity were analyzed after BUB1 and BUBR1 inhibition. Additionally, combinatorial effects of gene inhibition and radiation or Temozolomide (TMZ) treatment were evaluated through proliferation and clonogenic capacity assays. RESULTS: We report the upregulation of BUB1 and BUBR1 expression and the downregulation of BUB3 in GBM samples and cell lines when compared to white matter samples (p < 0.05). Decreased cell proliferation and colony formation after BUB1 and BUBR1 inhibition were observed, along with increased micronuclei formation. Combinations with TMZ also caused cell cycle arrest and increased apoptosis. Moreover, our results demonstrate that BUB1 and BUBR1 inhibition sensitized SF188 cells to γ-irradiation as shown by decreased growth and abrogation of colony formation capacity. CONCLUSION: BUB1 and BUBR1 inhibition decreases proliferation and shows radiosensitizing effects on pediatric GBM cells, which could improve treatment strategies for this devastating tumor. Collectively, these findings highlight the potentials of BUB1 and BUBR1 as putative therapeutic targets for glioblastoma treatment.

Drugging Hijacked Kinase Pathways in Pediatric Oncology: Opportunities and Current Scenario.

Childhood cancer is considered rare, corresponding to ~3% of all malignant neoplasms in the human population. The World Health Organization (WHO) reports a universal occurrence of more than 15 cases per 100,000 inhabitants around the globe, and despite improvements in diagnosis, treatment and supportive care, one child dies of cancer every 3 min. Consequently, more efficient, selective and affordable therapeutics are still needed in order to improve outcomes and avoid long-term sequelae. Alterations in kinases' functionality is a trademark of cancer and the concept of exploiting them as drug targets has burgeoned in academia and in the pharmaceutical industry of the 21st century. Consequently, an increasing plethora of inhibitors has emerged. In the present study, the expression patterns of a selected group of kinases (including tyrosine receptors, members of the PI3K/AKT/mTOR and MAPK pathways, coordinators of cell cycle progression, and chromosome segregation) and their correlation with clinical outcomes in pediatric solid tumors were accessed through the R2: Genomics Analysis and Visualization Platform and by a thorough search of published literature. To further illustrate the importance of kinase dysregulation in the pathophysiology of pediatric cancer, we analyzed the vulnerability of different cancer cell lines against their inhibition through the Cancer Dependency Map portal, and performed a search for kinase-targeted compounds with approval and clinical applicability through the CanSAR knowledgebase. Finally, we provide a detailed literature review of a considerable set of small molecules that mitigate kinase activity under experimental testing and clinical trials for the treatment of pediatric tumors, while discuss critical challenges that must be overcome before translation into clinical options, including the absence of compounds designed specifically for childhood tumors which often show differential mutational burdens, intrinsic and acquired resistance, lack of selectivity and adverse effects on a growing organism.

Cytogenetic findings in pediatric radiation-induced atypical meningioma after treatment of medulloblastoma: case report and review of the literature.

Ionizing radiation is the most recognized risk factor for meningioma in pediatric long-term cancer survivors. Information in this rare setting is exceptional. We report the clinical and cytogenetic findings in a radiation-induced atypical meningioma following treatment for desmoplastic medulloblastoma in a child. This is the second study to describe the cytogenetic aspects on radiation-induced meningiomas in children. Chromosome banding analysis revealed a 46, XX, t(1;3)(p22;q12), del(1)(p?)[8]/46, XX[12]. Loss of chromosome 1p as a consequence of irradiation has been proposed to be more important in the development of secondary meningiomas in adults. Deletions in the short arm of chromosome 1 also appear to be a shared feature in both pediatric cases so far analyzed.

In vitro PLK1 inhibition by BI 2536 decreases proliferation and induces cell-cycle arrest in melanoma cells.

Melanoma is one of the most treatment-resistant malignancies and regardless of new therapeutic tactics the outcome remains dismal. Polo-like kinase 1 (PLK1) has been shown to be over-expressed in a variety of tumors, becoming an attractive target for cancer management. In the present study we tested the in vitro antitumor activities of BI 2536, a selective inhibitor of PLK1, against two melanoma cell lines. Our results showed that nanomolar concentrations (10-150 nmol/L) of the drug significantly decreased cell proliferation and clonogenicity, promoting cell cycle arrest in G2/M. Targeting the cell cycle offers an attractive potential cancer-treatment option. Herein we show that PLK1 inhibition may be a feasible approach for the impairment of tumor progression and dissemination. This in vitro profile of melanoma cell growth inhibition by PLK1 modulation may be an interesting model to be tested in association with first-line antineoplasic agents in melanomas.

The Double Face of miR-708: A Pan-Cancer Player with Dissociative Identity Disorder.

Over the last decades, accumulating evidence has shown tumor-dependent profiles of miR-708, being either up- or downregulated, and thus, acting as a "Janus" regulator of oncogenic pathways. Herein, its functional duality was assessed through a thorough review of the literature and further validation in silico using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. In the literature, miR-708 was found with an oncogenic role in eight tumor types, while a suppressor tumor role was described in seven cancers. This double profile was also found in TCGA and GEO databases, with some tumor types having a high expression of miR-708 and others with low expression compared with non-tumor counterparts. The investigation of validated targets using miRBase, miRTarBase, and miRecords platforms, identified a total of 572 genes that appeared enriched for PI3K-Akt signaling, followed by cell cycle control, p53, Apellin and Hippo signaling, endocrine resistance, focal adhesion, and cell senescence regulations, which are all recognized contributors of tumoral phenotypes. Among these targets, a set of 15 genes shared by at least two platforms was identified, most of which have important roles in cancer cells that influence either tumor suppression or progression. In a clinical scenario, miR-708 has shown to be a good diagnostic and prognosis marker. However, its multitarget nature and opposing roles in diverse human tumors, aligned with insufficient experimental data and the lack of proper delivery strategies, hamper its potential as a sequence-directed therapeutic.

BI 2536-mediated PLK1 inhibition suppresses HOS and MG-63 osteosarcoma cell line growth and clonogenicity.

Osteosarcoma is the most common primary malignant tumor of bone, which frequently occurs in the second decade of life. Despite the improvements in neoadjuvant chemotherapy, the outcome of patients with chemoresistant or metastatic tumors is still poor. Therefore, there is a need for the development of more efficient therapeutic agents. BI 2536, an innovative selective inhibitor of Polo-like kinase 1, has shown anticancer potential promoting mitotic arrest and apoptosis in a variety of tumor cells, including osteosarcoma. Here, we present more evidence of the antiproliferative effects of BI 2536 on HOS and MG-63 osteosarcoma cell lines. Our results showed that nanomolar concentrations (10, 50, and 100 nmol/l) of the drug significantly decreased cell proliferation and clonogenic capacity, inducing mitotic arrest and aneuploidy. Interestingly, although BI 2536 mediated a moderate increase of apoptosis after 48 h in HOS cells, no increased caspase-3 activity was detected for MG-63 cells. In contrast to previous studies, we show that perturbation of normal mitotic progression by BI 2536 in these osteosarcoma cell lines results in caspase-independent mitotic catastrophe followed by necrosis. Our findings reinforce the likelihood of directing against Polo-like kinase 1 as a therapeutic option in the treatment of osteosarcoma.

MicroRNAs: understanding their role in gene expression and cancer.

MicroRNAs are small RNA molecules that regulate gene expression in cells. These small molecules comprise 17 to 25 nucleotides and are able to recognize target messenger RNAs by sequence complementarity and regulate their protein translation. Different microRNAs are expressed in all human cells. There is over 2,500 microRNAs described in humans that are involved in virtually all biological processes. Given their role as gene expression regulators, these molecules have been widely investigated and are thought to be associated with some specific physiological and pathological conditions, being proposed as biomarkers. It has recently been reported that microRNAs are secreted outside cells and are involved in intercellular communication. MicroRNAs in biological fluids are named circulating and have been detected in all body fluids, although the expression profile is specific for each type. The major advantages of using circulating microRNAs as biological markers are the high stability of those molecules and the wide availability of samples. Also, given the individual nature of microRNA expression changes, these molecules have a high potential for use in personalized medicine. In fact, microRNA expression profile determination may support disease recognition and diagnosis, and can be used to monitor therapeutic responses and establish patient prognosis, assisting in choice of treatment. This review provides a general overview of microRNAs and discusses the importance of those molecules in cancer, for deeper understanding of their role in this disease.

The Carbonic Anhydrase Inhibitor E7070 Sensitizes Glioblastoma Cells to Radio- and Chemotherapy and Reduces Tumor Growth.

Glioblastomas (GBMs), the most common and lethal primary brain tumor, show inherent infiltrative nature and high molecular heterogeneity that make complete surgical resection unfeasible and unresponsive to conventional adjuvant therapy. Due to their fast growth rate even under hypoxic and acidic conditions, GBM cells can conserve the intracellular pH at physiological range by overexpressing membrane-bound carbonic anhydrases (CAs). The synthetic sulfonamide E7070 is a potent inhibitor of CAs that harbors putative anticancer properties; however, this drug has still not been tested in GBMs. The present study aimed to evaluate the effects of E7070 on CA9 and CA12 enzymes in GBM cells as well as in the tumor cell growth, migration, invasion, and resistance to radiotherapy and chemotherapy. We found that E7070 treatment significantly reduced tumor cell growth and increased radio- and chemotherapy efficacy against GBM cells under hypoxia. Our data suggests that E7070 has therapeutic potential as a radio-chemo-sensitizing in drug-resistant GBMs, representing an attractive strategy to improve the adjuvant therapy. We showed that CA9 and CA12 represent potentially valuable therapeutic targets that should be further investigated as useful diagnostic and prognostic biomarkers for GBM tailored therapy.

Expression profiles and prognostic value of miRNAs in retinoblastoma.

Current cure rates for retinoblastoma (RB) are very high in developed countries. Nonetheless, in less privileged places worldwide, delayed diagnosis and refusal to adhere to treatment still endure an obstacle to improve overall patient survival. Thus, the access to consistent biomarkers for diagnosis at an earlier stage may facilitate treatment and improve outcomes. Over recent years, much attention has been focused on miRNAs, key post-transcriptional regulators that when altered, largely contribute to carcinogenesis and tumor progression. Many of the ~ 2500 microRNAs described in humans have shown differential expression profiles in tumors. In this review, we summarize current data about the roles of miRNAs in RB along with their value as diagnostic/prognostic factors using electronic databases such as PubMed. We reviewed the importance of miRNA in RB biology and discussed their implications in clinic intervention. Several miRNAs have pointed out reliable diagnostic and prognostic molecular biomarkers. The emergence of targeted therapies has significantly improved cancer treatment. In the near future, the modulation of miRNAs will represent a good treatment strategy.

G2/M inhibitors as pharmacotherapeutic opportunities for glioblastoma: the old, the new, and the future.

Glioblastoma (GBM) is one of the deadliest tumors and has a median survival of 3 months if left untreated. Despite advances in rationally targeted pharmacological approaches, the clinical care of GBM remains palliative in intent. Since the majority of altered signaling cascades involved in cancer establishment and progression eventually affect cell cycle progression, an alternative approach for cancer therapy is to develop innovative compounds that block the activity of crucial molecules needed by tumor cells to complete cell division. In this context, we review promising ongoing and future strategies for GBM therapeutics aimed towards G2/M inhibition such as anti-microtubule agents and targeted therapy against G2/M regulators like cyclin-dependent kinases, Aurora inhibitors, PLK1, BUB, 1, and BUBR1, and survivin. Moreover, we also include investigational agents in the preclinical and early clinical settings. Although several drugs were shown to be gliotoxic, most of them have not yet entered therapeutic trials. The use of either single exposure or a combination with novel compounds may lead to treatment alternatives for GBM patients in the near future.

TLE1 as an indicator of adverse prognosis in pediatric acute lymphoblastic leukemia.

PURPOSE: Acute lymphoblastic leukemia (ALL) is the most common type of cancer in children, and despite the high rate of cure (over 80%) it still has a big impact on morbidity and mortality. The Transducin-like enhancer of split 1 (TLE1), a transcriptional corepressor, has been described as dysregulated and recently emerged as a tumor marker in several cancer types, including hematologic malignancies. METHODS: In the present study TLE1 gene expression was evaluated by RT-qPCR. A total of 60 consecutive pathological ALL samples and 8 normal bone marrow samples were included. Associations between TLE1 levels and clinicopathological features were estimated using Mann-Whitney tests. RESULTS: TLE1 mRNA levels were significantly diminished in ALL samples when compared to normal counterparts (fold change -1.45, p-value 0.039). Lower TLE1 expression levels were associated with poorer prognostic features such as age at diagnosis (<1 or >9 years-old), absence of the Common Acute Lymphoblastic Leukemia Antigen (CALLA) and high white cell count. Considering immunophenotype, decreased expression of TLE1 was only evident for T-cell ALL, what was validated using gene expression profiling data available in public repositories. No associations with event or overall survival were observed. However, TLE1 expression was statistically different between patients who achieved complete clinical remission (CCR) from those that relapsed or died. CONCLUSION: These data are of particular interest and give support for a plausible role of TLE1 as a tumor suppressor in T-cell ALL. Moreover, the prognostic value of this corepressor may assist ALL treatment stratification and suggest the need of alternative regimens.

PLK1 Inhibition Radiosensitizes Breast Cancer Cells, but Shows Low Efficacy as Monotherapy or in Combination with other Cytotoxic Drugs.

BACKGROUND AND PURPOSE: Over the last decade, the inhibition of PLK1 has proven potent antiproliferative activity in vitro. However, the effectiveness of most synthetic targeted drugs has not yet been translated into clinics. Herein, we investigated the in vitro effects of two second-generation PLK1 inhibitors BI 6727 and GSK461364 in breast cancer cell lines as monotherapy or in combination with other drugs or ionizing radiation. MATERIAL AND METHODS: Cell survival was analyzed through XTT®, clonogenicity and caspase-3 activation assays were also studied, and drug interactions analyzed through a nonlinear regression of a sigmoid doseresponse model. Sensibilization to radiation was assessed through enhancement ratio calculation. RESULTS: Mild effects on the viability of both cell lines tested (MCF-7 and Hs578T) were observed irrespective of the used PLK1 inhibitor. Alternatively, abrogation of PLK1 significantly reduced clonogenicity while effectively sensitized cells to ionizing radiation. Drug interactions showed dissimilar results with antagonistic effects with any drug combination in MCF-7 and clear synergic interactions between both PLK1 inhibitors and cisplatin, temozolomide or doxorubicin in Hs578T, which is TP53 mutated. CONCLUSION: Targeting kinases involved in mitotic checkpoints are expected to prevent mitotic exit and enhance chemosensitization. Nonetheless, despite overexpressing PLK1, in our model, expressive results after its inhibition were only seen through clonogenic assays or when BI 6727 and GSK461364 were combined with ionizing radiation. Disparate responses of cell lines to drug combinations might denote a partial reflection of the substantial differences in the vast spectrum of genetic, biological and epigenetic burden observed in breast cancer. In the near future, individual genomic/proteomic profiling will allow its further classification and will consent the initiation of novel strategies for therapy. Even though the future impact of PLK1-tailored treatment still needs validation, much more pre-clinical and clinical research for this kinase are warranted.

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

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.