Abstract
Neuroblastoma (NB) is a common malignant solid tumor in children and accounts for 15% of childhood cancer mortality. Amplification of the N-Myc oncogene is a well-established poor prognostic marker in NB patients and strongly correlates with higher tumor aggression and resistance to treatment. New therapies for patients with N-Myc-amplified NB need to be developed. After treating NB cells with BSAO/SPM, the detection of apoptosis was determined after annexin V-FITC labeling and DNA staining with propidium iodide. The mitochondrial membrane potential activity was checked, labeling cells with the probe JC-1 dye. We analyzed, by real-time RT-PCR, the transcript of genes involved in the apoptotic process, to determine possible down- or upregulation of mRNAs after the treatment on SJNKP and the N-Myc-amplified IMR5 cell lines with BSAO/SPM. The experiments were carried out considering the proapoptotic genes Tp53 and caspase-3. After treatment with BSAO/SPM, both cell lines displayed increased mRNA levels for all these proapoptotic genes. Western blotting analysis with PARP and caspase-3 antibody support that BSAO/SPM treatment induces high levels of apoptosis in cells. The major conclusion is that BSAO/SPM treatment leads to antiproliferative and cytotoxic activity of both NB cell lines, associated with activation of apoptosis.
Highlights
Neuroblastoma is the most frequent solid tumor of the childhood
We showed that treatment with bovine serum amine oxidase (BSAO)/SPM induced apoptosis in NB cells, via activation of p53, increased miRNA
34a expression, and promoted mitochondrial membrane depolarization in the N-Mycamplified neuroblastoma cell line. These findings suggest that the proposal of a novel therapeutic approach using the combinatorial treatment with BSAO/SPM may be taken into account
Summary
Neuroblastoma is the most frequent solid tumor of the childhood. It represents 6–10%of all pediatric tumors, and its occurrence after five years of age is a very rare event [1,2].Neuroblastoma cells derive from the embryonic neural crest, and the tumor can be localized in adrenal medulla or in any area of the sympathetic nervous system [3]. The International Neuroblastoma Risk Group (INRG) has developed a classification system for neuroblastoma risk stratification based on clinical criteria, including stage, histology, differentiation, ploidy, alterations at chromosome 11q, and amplification of MYCN [8]. This classification allows to divide patient groups into favorable or unfavorable subsets. A new therapeutical approach for unfavorable patients is needed [14] In this regard, a recent novel strategy for anticancer therapy using polyamines is under investigation [1,15]
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