Journal
CELLS
Volume 10, Issue 8, Pages -Publisher
MDPI
DOI: 10.3390/cells10081950
Keywords
polyamine; neuroblastoma; apoptosis; microRNA; mitochondria; reactive oxygen species; oncotherapy
Categories
Funding
- La Sapienza University of Rome
- Italian MIUR (Ministero dell'Istruzione, dell'Universita e della Ricerca), Dipartimenti di Eccellenza [232/2016]
- AIRC [IG 17575, IG 20801]
- Istituto Pasteur-Fondazione Cenci-Bolognetti, AFM-Telethon [21025]
- Wakunaga Pharmaceutical Co. Ltd. (Japan)
- FIRC/AIRC Michele e Carlo Ardizzone fellowship
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Neuroblastoma is a common malignant solid tumor in children, with N-Myc amplification being a poor prognostic marker in NB patients. Treatment with BSAO/SPM leads to increased mRNA levels of proapoptotic genes in NB cell lines, inducing apoptosis activity.
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.
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