MMP-2 expression and secretion are increased in SHEP neuroblastoma cells expressing Bcl-2 alone (SHEP/Bcl-2 cells) or both N-Myc and Bcl-2 (SHEP/N-Myc/Bcl-2 cells).
It was hypothesized that the expression of proapoptotic (Bax) and prosurvival (Bcl-2 and Mcl-1) proteins would be altered in neuroblastoma cells grown in a cell culture model of metastatic neuroblastoma.
The up-regulation of thioredoxin may be a compensating mechanism for cell survival in neuroblastoma when Bcl-2 expression is suppressed, and it may to some extent attenuate the effectiveness of antisense bcl-2 therapy.
For example, miR-15 and miR-16 induce apoptosis by targeting Bcl2. miRNAs from the miR-17-92 cluster modulate tumor formation and function as oncogenes by influencing the translation of E2F1 mRNA. miR-21 modulates gemcitabine-induced apoptosis by phosphatase and tensin homolog deleted on chromosome 10-dependent activation of PI 3-kinase signaling. miR-34a acts as a suppressor of neuroblastoma tumorigenesis by targeting the mRNA encoding E2F3 and reducing E2F3 protein levels.
There was a significant reduction in p53, p21(WAF1) and Ki67 LI after chemotherapy (p < 0.01), an increase in BAX (p <0.05), but no change in Bcl2. p53 localization and function were examined in two p53 wild-type undifferentiated and 9-cis retinoic acid differentiated neuroblastoma cell lines.
We conditionally activated N-myc in SH-EP neuroblastoma cells subjected to the trophic stress of serum or nutrient deprivation while changing the expression of Bcl-2, survivin and FLIP(L), antiapoptotic molecules often overexpressed in poor prognosis neuroblastomas.
Neuroblastoma and brain tumor cell lines are particularly sensitive to neocarzinostatin; the sensitivity of brain tumor lines to neocarzinostatin is enhanced by transfection with an expression construct for Bcl-2 and is proportional in transfected cells to the product of the relative contents of Bcl-2 and caspase-3 (r (2) = 0.7).
The study to elucidate the cytotoxic mechanisms of compound 1, the most potent diarylheptanoid showed that cell cycle-related proteins, cyclins, CDKs and CDKIs, as well as two main apoptotic related families, caspase and Bcl 2 were involved in S phase arrest and apoptosis in neuroblastoma cell line SH-SY5Y.
Furthermore, the effects of Aβ and TD/GH on LDH release, apoptosis and its relevant gene expression, involving bcl-2 and bax/caspase-3, were observed in a human neuroblastoma cell line (SH-SY5Y).
In addition, experiments based on siRNA transfections were performed in the human SH-SY5Y neuroblastoma cell line to verify that the stability of Bcl-2 is causal to neuronal survival.
Thus, combining 13-cis-RA with cytotoxic chemotherapy significantly reduced the cytotoxicity for neuroblastoma in vitro, mediated at least in part via the antiapoptotic Bcl-2 family of proteins.
On the basis of our results, it appears that ellipticine resistance in neuroblastoma is caused by a combination of overexpression of Bcl-2, efflux or degradation of the drug and downregulation of topoisomerases.
Identical results were obtained by treatment of the neuroblastoma cell lines with the small molecule BCL2 inhibitor ABT263, which is currently being clinically evaluated.
The single chain antibody encoded targeted polyplex was more effective in transferring Bcl-2 siRNA than the nontargeting one in SK-N-SH cells, a human neuroblastoma cell line, resulting in a 46.34% inhibition in the expression of Bcl-2 mRNA.
Human neuroblastoma cells (SH-SY5Y) were exposed to isatin at various concentrations (0, 50, 100, 200 μmol/l) for 48 h. Bcl-2 and Bax mRNA were analyzed via RT-PCR.
LSD1 protein expression levels were assessed semi-quantitatively in specimens of NB and ganglioneuroblastoma (GNB), along with the apoptosis markers, Bcl-2 and Bax.
By serendipity we cloned a variant of the anti-apoptotic Bcl2-family member Myeloid cell leukemia-1 (Mcl1) from human neuroblastoma and leukemia cells.
We showed that SART1 knockdown similarly sensitized Mcl1-dependent NB to ABT-737 and that triple knockdown of UBL5/PRPF8/SART1 phenocopied direct MCL1 knockdown, whereas having no effect on Bcl2-dependent NBs.