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Enzymatic Spermine Metabolites Induce Apoptosis Associated with Increase of p53, caspase-3 and miR-34a in Both Neuroblastoma Cells, SJNKP and the N-Myc-Amplified Form IMR5.
- Source :
-
Cells [Cells] 2021 Jul 31; Vol. 10 (8). Date of Electronic Publication: 2021 Jul 31. - Publication Year :
- 2021
-
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.
- Subjects :
- Animals
Caspase 3 genetics
Cell Line, Tumor
Cell Proliferation drug effects
Gene Amplification
Gene Expression Regulation, Neoplastic
Humans
Membrane Potential, Mitochondrial drug effects
MicroRNAs genetics
N-Myc Proto-Oncogene Protein genetics
Neuroblastoma enzymology
Neuroblastoma genetics
Rats, Wistar
Signal Transduction
Spermine metabolism
Tumor Suppressor Protein p53 genetics
Rats
Amine Oxidase (Copper-Containing) pharmacology
Antineoplastic Combined Chemotherapy Protocols pharmacology
Apoptosis drug effects
Caspase 3 metabolism
MicroRNAs metabolism
N-Myc Proto-Oncogene Protein metabolism
Neuroblastoma drug therapy
Spermine pharmacology
Tumor Suppressor Protein p53 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2073-4409
- Volume :
- 10
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Cells
- Publication Type :
- Academic Journal
- Accession number :
- 34440719
- Full Text :
- https://doi.org/10.3390/cells10081950