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.
Mechanistically treatment of NBs with small molecule inhibitors of EGFR (erlotinib, cetuximab) and ERK (U0126) increases Noxa expression and dephosphorylates Bim to promote Bim binding to Bcl(-)2.
We demonstrate that SV infection of baby hamster kidney (BHK-2), mouse neuroblastoma (N18), and rat prostatic adenocarcinoma (AT-3) cells results in programmed cell death, whereas SV infection of bcl-2-transfected AT-3 cells results in long-term persistent productive infection.
Recently, immunoreactivity to the bcl-2 gene product has been reported not only in a variety of embryonal and adult nonhematopoietic tissues, but also in neuroblastoma.
We investigated the expression of the, bcl-2 proto-oncogene in untreated cases of neuroblastoma. bcl-2 is a novel proto-oncogene that promotes cell growth by inhibiting programmed cell death (apoptosis), a form of cellular demise common during normal neurogenesis.
To further explore whether S-nitrosylation of Bcl-2 involved in Mn-induced autophagy dysregulation, we treated human neuroblastoma (SH-SY5Y) cells with Mn and pretreated cells with 1400 W, a selective iNOS inhibitor.
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.
Identical results were obtained by treatment of the neuroblastoma cell lines with the small molecule BCL2 inhibitor ABT263, which is currently being clinically evaluated.
Overall, our results demonstrate the therapeutic potential of CXCR4 inhibition in neuroblastoma treatment and provide a rationale to test combination therapies employing CXCR4 and BCL-2 inhibitors to increase the efficacy of these agents.<b>Significance:</b> These results provide a mechanistic rationale for combination therapy of CXCR4 and BCL-2 inhibitors to treat a common and commonly aggressive pediatric cancer.<i></i>.
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.
LSD1 protein expression levels were assessed semi-quantitatively in specimens of NB and ganglioneuroblastoma (GNB), along with the apoptosis markers, Bcl-2 and Bax.
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.
GX15-070 (Obatoclax), a Bcl-2 family proteins inhibitor engenders apoptosis and pro-survival autophagy and increases Chemosensitivity in neuroblastoma.
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.
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.