Nuclear factor‐κB activation and differential expression of survivin and Bcl‐2 in human grade 2–4 astrocytomas

Angileri, Filippo Flavio; Aguennouz, M.; Conti, Alfredo; Torre, Domenico La; Cardali, Salvatore; Crupi, Rosalia; Tomasello, Chiara; Germanò, Antonino; Vita, Giuseppe; Tomasello, Francesco

doi:10.1002/cncr.23407

Cited by 73 publications

(59 citation statements)

References 52 publications

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“…As supposed, Bcl-2 expression is upregulated in BGSCs, either at transcriptional or translational level. Bcl-2 has been found overexpressed in gliomas and considered a responsible factor for glioma resistance to apoptosis-related therapies (4,33,36,45), and our results proved that Bcl-2 is overexpressed in BGSCs either. Furthermore, Bcl-2 expression levels are higher in BGSCs than in PGCs, indicating that BGSCs may have more opportunities than PGCs to evade apoptosis induced by adjuvant treatments.…”

Section: Discussionsupporting

confidence: 64%

“…Defects in the regulation of apoptotic cell death contribute to the genesis and progression of gliomas. Failure to trigger the cellular suicide program not only predisposes to development of malignancies, but also increases the resistance of gliomas to anticancer drugs and irradiation (33). Apoptosis is a tightly regulated form of programmed cell death involving a series of biochemical events (34)(35)(36), in which Bcl-2 gene has been proved to play a critical role in the key events of mitochondrial apoptosis (37)(38)(39).…”

Section: Discussionmentioning

confidence: 99%

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Expression and correlation of Bcl-2 with pathological grades in human glioma stem cells

2012

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Abstract. The anti-apoptotic gene, B-cell lymphoma-2 (Bcl-2), has been reported to be overexpressed in gliomas and is related to tumor prognosis, suggesting a potential therapeutic target. Additionally, recent studies have demonstrated the existence of brain glioma stem cells (BGSCs) which are tumorigenic, selfrenewable and dominate the biological behavior of gliomas. Currently BGSCs are committed as a new target of glioma therapies. However, few studies have focused on the expression of Bcl-2 in BGSCs. We performed a series of experiments to culture BGSCs from eight clinical specimens, followed by real-time RT-PCR and immunoassays to compare the expression levels of Bcl-2 in BGSCs and their corresponding primary glioma cells (PGCs). The results showed that Bcl-2 mRNA and protein expression levels are higher in BGSCs compared to their counterparts, and the expression levels are related to glioma malignancies. As an anti

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Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Expression and correlation of Bcl-2 with pathological grades in human glioma stem cells

2012

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“…They were shown to escape apoptosis by (i) over-expressing anti-apoptotic proteins of the BCL-2 family such as BCL-2 and BCL-XL, but down-regulating the pro-apoptic Bax [34], (ii) expressing the BCL2-like 12 protein (BCL2L12), an inhibitor of caspase-3 and caspase-7 [35,36] and (iii) expressing high levels of IAP proteins [37,38].…”

Section: Discussionmentioning

confidence: 99%

NF-kappaB inhibition improves the sensitivity of human glioblastoma cells to 5-aminolevulinic acid-based photodynamic therapy

Coupienne

Bontems

Dewaele

et al. 2011

Biochemical Pharmacology

101

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To cite this version:Isabelle Coupienne Isabelle Coupienne, Sébastien Bontems, Michael Dewaele, Noemi Rubio, Yvette Habraken, et al.. NF-kappaB inhibition improves the sensitivity of human glioblastoma cells to 5-aminolevulinic acid-based photodynamic therapy. Biochemical Pharmacology, Elsevier, 2011, 81 (5) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 2 AbstractGlioblastoma constitute the most frequent and deadliest brain tumors of astrocytic origin.They are very resistant to all current therapies and are associated with a huge rate of recurrence. In most cases, this type of tumor is characterized by a constitutive activation of the nuclear factor-kappaB (NF-B). This factor is known to be a key regulator of various physiological processes such as inflammation, immune response, cell growth or apoptosis. In the present study, we explored the role of NF-B activation in the sensitivity of human glioblastoma cells to a treatment by 5-aminolevulinic acid (5-ALA)-based photodynamic therapy (PDT). 5-ALA is a physiological compound widely used in PDT as well as in tumor photodetection (PDD). Our results show that inhibition of NF-κB improves glioblastoma cell death in response to 5-ALA-PDT. We then studied the molecular mechanisms underlying the cell death induced by PDT combined or not with NF-B inhibition. We found that apoptosis was induced by PDT but in an incomplete manner and that, unexpectedly, NF-B inhibition reduced its level. Oppositely PDT mainly induces necrosis in glioblastoma cells and NF-B is found to have anti-necrotic functions in this context. The autophagic flux was also enhanced as a result of 5-ALA-PDT and we demonstrate that stimulation of autophagy acts as a prosurvival mechanism confering protection against PDT-mediated necrosis. These data point out that 5-ALA-PDT has an interesting potential as a mean to treat glioblastoma and that inhibition of NF-B renders glioblastoma cells more sensitive to the treatment.

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“…In the majority of primary nervous system tumors, particularly in glioblastomas and peripheral nerve sheath tumors survivin is also expressed (29). In glioblastomas, positive survivin expression was seen in immunohistochemistry and detected in high levels throughout the specimens, with a positive correlation to the Ki-67 proliferation index (30,31). However, no correlation between the intensity of survivin staining and the clinical course of the tumors has been seen (29).…”

Section: Discussionmentioning

confidence: 99%

Evidence of ubiquitous in vivo and in vitro expression of pro-apoptotic Smac/DIABLO protein in meningioma cell lines

Pfister

Ritz²,

Endemann³

et al. 2009

Oncol Rep

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Abstract. Although meningiomas are one of the most common tumors in the central nervous system, the adjuvant treatment for recurrent or malignant meningiomas is not satisfactory. An intense interest in evaluating new molecular markers that may serve as potential therapeutic targets exists. Changes in apoptosis mechanisms play important roles in tumor pathogenesis. One pro-apoptotic protein is Smac/DIABLO, which neutralizes the inhibitors of apoptosis (IAPs). As Smac/ DIABLO has not been previously analyzed in meningiomas, We investigated the expression of Smac/DIABLO and survivin in primary meningioma cultures in vivo and in vitro. Expression of Smac/DIABLO, survivin and single-stranded (ss)DNA in vivo were determined immunohistochemically in 100 meningioma surgical specimens, dura and normal human cortex. The expression of the apoptotic enzymes in vitro was analyzed after RNA and protein isolation of all meningiomas via Western blotting and PCR. All examined meningiomas and normal cerebral cortex displayed intense positive cytoplasmic Smac/DIABLO immuno-reactivity. Survivin and ssDNA were expressed in all surgical specimens and showed weak staining overall. Examination of Smac/DIABLO protein via Western blotting showed distinct signals in the cytoplasmic extracts. PCR analysis displayed no changes of Smac/DIABLO and survivin expression in different meningioma grades, normal human cortical cortex or dura. Constant high-level Smac/DIABLO respectively low-level survivin expression in meningiomas and normal brain demonstrate similar apoptotic behavior of meningiomas compared to normal brain tissue. These findings indicate no pathological overexpression of survivin in meningiomas as is evident in several other cancer types impeding apoptosis.

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Nuclear factor‐κB activation and differential expression of survivin and Bcl‐2 in human grade 2–4 astrocytomas

Cited by 73 publications

References 52 publications

Expression and correlation of Bcl-2 with pathological grades in human glioma stem cells

Expression and correlation of Bcl-2 with pathological grades in human glioma stem cells

NF-kappaB inhibition improves the sensitivity of human glioblastoma cells to 5-aminolevulinic acid-based photodynamic therapy

Evidence of ubiquitous in vivo and in vitro expression of pro-apoptotic Smac/DIABLO protein in meningioma cell lines

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