4-HPR + ABT-199 was highly synergistic against high BCL-2-expressing neuroblastoma cell lines and significantly improved event-free survival of mice carrying high BCL-2-expressing patient-derived xenografts (PDX).
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).
By serendipity we cloned a variant of the anti-apoptotic Bcl2-family member Myeloid cell leukemia-1 (Mcl1) from human neuroblastoma and leukemia cells.
Collectively, these results suggest that IGF-IR or Bcl-2 overexpression in neuroblastoma cells promotes cell survival by preventing mitochondrial membrane depolarization and caspase-3 activation, ultimately leading to increased tumor growth.
Disrupted mitochondrial electron transport function increases expression of anti-apoptotic bcl-2 and bcl-X(L) proteins in SH-SY5Y neuroblastoma and in Parkinson disease cybrid cells through oxidative stress.
Ectopic expression of LGP2 in NB cells significantly enhanced poly (I:C)-induced NB cell death associated with downregulation of MDA5, RIG-I, MAVS and Bcl-2, as well as upregulation of Noxa and tBid.
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.
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).
Furthermore, whole-genome transcriptome analysis revealed that BRG1 controls the expression of key elements of oncogenic pathways such as PI3K/AKT and BCL2, which offers a promising new combination therapy for high-risk NB.
GX15-070 (Obatoclax), a Bcl-2 family proteins inhibitor engenders apoptosis and pro-survival autophagy and increases Chemosensitivity in neuroblastoma.
However, combined treatment with bcl-2 and FLIP antisense oligonucleotides had a statistically significant synergistic effect reversing Fas-resistance in neuroblastoma cells in vitro.
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.
Identical results were obtained by treatment of the neuroblastoma cell lines with the small molecule BCL2 inhibitor ABT263, which is currently being clinically evaluated.
In <i>MYCN</i>-amplified neuroblastoma, PUMA induction by GSK-J4 sensitized tumors to the B cell lymphoma 2 (BCL-2) inhibitor venetoclax, demonstrating that epigenetic-targeted therapies and BCL-2 homology domain 3 mimetics can be rationally combined to treat this high-risk subset of neuroblastoma.
In addition to NBs, lower levels of BCL2 protein were also found in a variety of other neural crest-derived tumors and tumor cell lines, including some neuroepitheliomas, Ewing's sarcomas, neurofibromas, and melanomas.
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.