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

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.

Anticancer Cytotoxic Activity of Bispidine Derivatives Associated with the Increasing Catabolism of Polyamines

“…Our study is in accordance with the recent work by Kanamori et al [42], who demonstrated that exogenous bovine serum amine oxidase and PA could induce apoptosis in cancer but not normal cells. However, we aimed to enhance the same PA-degrading pathway using small molecule drug substances to activate endogenous enzymes of PAs catabolism.…”

Programmed Cell Death Reversal: Polyamines, Effectors of the U-Turn from the Program of Death in Helianthus tuberosus L.

“…In fact, most of the radioactivity is released from proteins (35-55%) and to a lesser extent from NA. RNase mainly releases Spm, whereas DNase releases mainly Spd with respect to the other two PAs[22,23]. Spm and Put were the main PAs bound to rRNA or to tRNA.…”

“…These biogenic amines are ubiquitous across almost all living cells, from bacteria to plant and animal phyla, and are essential for life. In plants, the regulatory role in PCD of the main three aliphatic PAs, i.e., putrescine (Put), spermidine (Spd) and spermine (Spm), is reported by several articles [8,9,[15][16][17][18][19][20][21][22].…”

Bovine Serum Amine Oxidase and Polyamine Analogues: Chemical Synthesis and Biological Evaluation Integrated with Molecular Docking and 3-D QSAR Studies

“…In particular, the PA biosynthetic pathway is very active during cancer cell growth, and PA content is increased in tumor cells and tissues, such as breast, colon, skin, and prostate cancers. , Given the role of natural PAs in cancer, efforts have been made in search for strategies that target the PA metabolism, which might be useful for tumor treatment. , In this context, the main investigated strategies have been pointed to reduce intracellular PA concentration by inhibition of their synthesis or transport across cell membranes as well as through the use of analogues that interfere with PA metabolism. More recently, the strategy of exploiting PA-degrading enzymes to induce cancer cells death has been applied. , Indeed, the oxidative deamination of PAs catalyzed by some amine oxidases causes an over-production of aldehydes and hydrogen peroxide, which are cytotoxic and can damage cancer cells, causing apoptosis/necrosis and ultimately cell death. − The induction of oxidative stress by increasing ROS has recently received great attention in anticancer therapies, and the effect of various anticancer drugs is based on the principle of oxidative stress-induced chemotherapy; for example, 2-methoxyestradiol induces mitochondrial production of hydrogen peroxide and subsequently activates c-Jun N-terminal kinase (JNK), resulting in apoptosis initiation …”