The NF-κB pathway mediates fenretinide-induced apoptosis in SH-SY5Y neuroblastoma cells

Hewson, Q D Campbell; Lovat, Penny E.; Corazzari, Marco; Catterall, J.; Redfern, Christopher P.F.

doi:10.1007/s10495-005-1878-z

Cited by 23 publications

(14 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…17 For example, we previously reported that activation of NF-jB by the natural compound betulinic acid contributes to betulinic acid-induced apoptosis in neuroblastoma cells. 18 Also, NF-jB was shown to mediate fenretinide-or doxorubicin-induced apoptosis in neuroblastoma cells 35,36 and to repress the expression of certain antiapoptotic genes in response to atypical NF-jB inducers, that is, daunorubicin, cisplatin and UV-C irradiation. 30,37 Together, these data support the concept that the role of NF-jB in the regulation of apoptosis depends on the context, that is, stimulus, cell line and/or cell type.…”

Section: Context-dependent Function Of Nf-jb In Neuroblastomamentioning

confidence: 99%

Sensitization of neuroblastoma cells for TRAIL‐induced apoptosis by NF‐κB inhibition

Ammann

Haag

Kasperczyk

et al. 2008

Intl Journal of Cancer

View full text Add to dashboard Cite

The transcription factor nuclear factor‐kappaB (NF‐κB) plays a central role in stress‐induced transcriptional activation and has been implicated in chemoresistance of cancers. In the present study, we investigated the role of NF‐κB in inducible chemoresistance of neuroblastoma. Doxorubicin, VP16 and the cytotoxic ligand TRAIL trigger NF‐κB activation, whereas cisplatin and taxol have no impact on NF‐κB activity. Specific inhibition of NF‐κB activation by overexpression of dominant‐negative mutant IκBα‐super‐repressor does not alter cell death upon doxorubicin or VP16 treatment, although it prevents doxorubicin‐ or VP16‐mediated NF‐κB activation. By comparison, inhibition of TRAIL‐stimulated NF‐κB activation by IκBα‐superrepressor or the small molecule NF‐κB inhibitor BMS‐345541 significantly enhances TRAIL‐induced apoptosis, pointing to an antiapoptotic function of NF‐κB in TRAIL‐mediated apoptosis. Analysis of signaling pathways reveals that NF‐κB inhibition prevents TRAIL‐triggered up‐regulation of Mcl‐1, promoting TRAIL‐induced cytochrome c release and activation of caspases. Accordingly, knockdown of Mcl‐1 by RNA interference significantly enhances TRAIL‐induced apoptosis and also increases sensitivity of neuroblastoma cells to CD95‐ or chemotherapy‐induced apoptosis. In conclusion, NF‐κB regulates apoptosis in a stimulus‐specific manner in neuroblastoma cells and confers protection against TRAIL‐induced apoptosis. By demonstrating that NF‐κB inhibition sensitizes neuroblastoma cells for TRAIL‐induced apoptosis, our findings have important implications. Thus, NF‐κB inhibitors may open new perspectives to potentiate the efficacy of TRAIL‐based protocols in the treatment of neuroblastoma. © 2008 Wiley‐Liss, Inc.

show abstract

Section: Context-dependent Function Of Nf-jb In Neuroblastomamentioning

confidence: 99%

Sensitization of neuroblastoma cells for TRAIL‐induced apoptosis by NF‐κB inhibition

Ammann

Haag

Kasperczyk

et al. 2008

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…Elevated NF-κB activation in cancer cells promotes tumor survival and progression [19–21]. In NB, the up-regulation of NF-κB has been shown to accelerate tumor growth and promote cancer cell survival [1, 19, 22, 23]. The blockade of NF-κB activation in cancer cells has been suggested to be a potential therapeutic strategy [24, 25].…”

Section: Introductionmentioning

confidence: 99%

Second-generation proteasome inhibitor carfilzomib sensitizes neuroblastoma cells to doxorubicin-induced apoptosis

Guan

Zhao

et al. 2016

Oncotarget

View full text Add to dashboard Cite

Neuroblastoma (NB), which accounts for about 15% of cancer-related mortality in children, is the most common extracranial malignant neoplasm in children. Elevated level of proteasome activity promotes cancer development and the inhibition of proteasome activity is a promising strategy for cancer treatment. Therefore, targeting proteasome by small molecule inhibitors may be a viable option for NB therapy. Here in this study, we show that a novel proteasome inhibitor Carfilzomib (CFZ) exerts anti-tumor effect on NB. CFZ caused decreased cell viability and attenuated colony formation ability of a subset of NB cell lines. CFZ induced cell apoptosis in NB cells. Moreover, CFZ enhanced the cytotoxic effect of doxorubicin (Dox) on NB cells and Dox-induced p38 and JNK phosphorylation. In addition, CFZ inhibited Dox-induced NF-κB activation by stabilizing the protein level of IκBα. Furthermore, CFZ induced apoptosis and augmented Dox-induced apoptosis in NB tumor cells in orthotopic xenograft mouse models. In summary, our study suggests that proteasome is a therapeutic target in NB and proteasome inhibition by CFZ is a potential therapeutic strategy for treating NB patients.

show abstract

“…Previous studies reported that 4-HPR [3, 23] or GST [12]induced apoptosis in a variety of cell linesincluding neuroblastoma [4, 12] with activation of caspase-3. The synergistic efficacy of 4-HPR + GST activated multiple pathways for increasing apoptosis, as suggested by molecular and histological observations, in two preclinical neuroblastoma animal models such as ectopic SH-SY5Y and orthotopic SK-N-BE2 xenografts.…”

Section: Discussionmentioning

confidence: 99%

“…Fenretinide or N-(4-hydroxyphenyl) retinamide (4-HPR), a synthetic retinoid, has shown the most promising broad spectrum anti-cancer efficacy against a variety of in vitro and in vivo animal studies [2], and chemopreventive clinical trials [3]. Notably, 4-HPR showed low toxicity and anti-tumor efficacy even in all- trans retinoic acid (ATRA) or 13- cis retinoic acid (13-CRA) resistant cancer cells; and several in vitro studies reported that dose-dependent anti-tumor efficacy of 4-HPR was mainly due to growth arrest and apoptosis in neuroblastoma [3, 4]. Treatment of neuroblastoma patients with high dose of 4-HPR accumulated a plasma 4-HPR concentration that was able to induce apoptosis in neuroblastoma cells [5].…”

Section: Introductionmentioning

confidence: 99%

Induction of Mitochondrial Pathways and Endoplasmic Reticulum Stress for Increasing Apoptosis in Ectopic and Orthotopic Neuroblastoma Xenografts

Karmakar¹,

Choudhury²,

Banik³

et al. 2011

JCT

View full text Add to dashboard Cite

Cancers are characterized by dysregulation of multiple signaling pathways and thus monotherapies are hardly effective. Neuroblastoma, which often occurs in adrenal glands, is the most common childhood malignancy. Malignant neuroblastoma resists traditional treatments and further studies are needed for effective therapeutic interventions. We evaluated synergistic efficacy of N-(4-hydroxyphenyl) retinamide (4-HPR) and genistein (GST) for induction of apoptosis in human malignant neuroblastoma SH-SY5Y and SK-N-BE2 cells in culture and activation of multiple pathways for increasing apoptosis in ectopic and orthotopic neuroblastoma xenografts in nude mice. Combination of 4-HPR and GST synergistically reduced cell viability, caused subG1 accumulation, increased caspase-3 activity for apoptosis in vitro and reduced tumor growth in vivo. Western blotting indicated that combination therapy down regulated Id2 to induce differentiation, increased pro-apoptotic Bax and decreased anti-apoptotic Bcl-2 leading to an increase in Bax:Bcl-2 ratio, increased mitochondrial Bax level, caused mitochondrial release of Smac/Diablo, down regulation of the baculovirus inhibitor-of-apoptosis repeat containing (BIRC) proteins such as BIRC-2 and BIRC-3, and activation of calpain and caspase-3 in SH-SY5Y xenografts. Accumulation of apoptosis-inducing-factor (AIF) in cytosol and increase in caspase-4 activation suggested involvement of mitochondrial pathway and endoplasmic reticulum (ER) stress, respectively, for apoptosis in SH-SY5Y xenografts. In situ immunofluorescent labelings of SH-SY5Y and SK-N-BE2 xenograft sections showed overexpression of calpain, caspase-12, and caspase-3, and AIF, suggesting induction of mitochondrial caspase-dependent and caspase-independent pathways for apoptosis. Collectively, synergistic effects of 4-HPR and GST induced mitochondrial pathways and also ER stress for increasing apoptosis in ectopic and orthotopic neuroblastoma xenografts in nude mice.

show abstract

The NF-κB pathway mediates fenretinide-induced apoptosis in SH-SY5Y neuroblastoma cells

Cited by 23 publications

References 29 publications

Sensitization of neuroblastoma cells for TRAIL‐induced apoptosis by NF‐κB inhibition

Sensitization of neuroblastoma cells for TRAIL‐induced apoptosis by NF‐κB inhibition

Second-generation proteasome inhibitor carfilzomib sensitizes neuroblastoma cells to doxorubicin-induced apoptosis

Induction of Mitochondrial Pathways and Endoplasmic Reticulum Stress for Increasing Apoptosis in Ectopic and Orthotopic Neuroblastoma Xenografts

Contact Info

Product

Resources

About