Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Aug;104(1):169-77.
doi: 10.1007/s11060-010-0496-y. Epub 2010 Dec 16.

Inhibition of NF-κB Signaling Commits Resveratrol-Treated Medulloblastoma Cells to Apoptosis Without Neuronal Differentiation

Affiliations

Inhibition of NF-κB Signaling Commits Resveratrol-Treated Medulloblastoma Cells to Apoptosis Without Neuronal Differentiation

Shu Wen et al. J Neurooncol. .

Abstract

Resveratrol promotes differentiation and apoptosis of medulloblastoma cells by suppressing STAT3 signaling and a range of cancer-associated gene expression. However, Bcl-2, a common target of STAT3 and NF-κB signaling, is distinctly up-regulated in resveratrol-treated medulloblastoma cells, indicating potential effects of NF-κB in Bcl-2 expression and anti-medulloblastoma efficiency of resveratrol. To clarify this point, the status of NF-κB signaling and the consequence of NF-κB inhibition in UW228-2 and UW228-3 medulloblastoma cells without and with resveratrol treatment were evaluated by several experimental approaches. The results revealed that resveratrol activated NF-κB signaling in both cell lines at the 4-h treatment point, and the treated cells sequentially exhibited Bcl-2 up-regulation, neuronal-like phenotype with synaptophisin expression, and, eventually, apoptosis. Pyrrolidine dithiocarbamate (PDTC) treatment inhibited NF-κB activation and Bcl-2 expression and committed resveratrol-treated cells to apoptosis at the 8-h time point without the step of neuron-oriented differentiation. On the other hand, a single 50 μg/ml lipopolysaccharide (LPS) treatment activated NF-κB signaling accompanied with sustained proliferation and neuron-like differentiation. Tissue microarray-based immunohistochemical staining showed significantly different (P < 0.001) p65 nuclear translocation between the neurons of tumor-surrounding cerebella (10/10; 100%) and medulloblastoma tissues (20/117; 17.09%). Additionally, synaptophysin production was found in 83.64% of p65-positive and in 40.35% of p65-negative medulloblastoma cases. Our in-vitro and in-vivo results thus demonstrate the dual effects of NF-κB signaling on medulloblastoma cells by delaying resveratrol-induced apoptosis by up-regulating Bcl-2 expression or by involvement in neuronal-like differentiation in the absence of resveratrol. Therefore, appropriate inhibition of NF-κB activation may enhance the anti-medulloblastoma efficacy of resveratrol.

Similar articles

See all similar articles

Cited by 11 articles

See all "Cited by" articles

References

    1. Int J Mol Med. 2003 Sep;12(3):299-304 - PubMed
    1. J Neurooncol. 2007 Sep;84(3):263-7 - PubMed
    1. Trends Mol Med. 2005 Jan;11(1):17-22 - PubMed
    1. J Neurooncol. 2009 Aug;94(1):51-6 - PubMed
    1. Mol Cell. 2002 Mar;9(3):625-36 - PubMed

Publication types

MeSH terms

LinkOut - more resources

Feedback