HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Inhibition of NF-κB signaling commits resveratrol-treated medulloblastoma cells to apoptosis without neuronal differentiation.

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.
AuthorsShu Wen, Hong Li, Mo-Li Wu, Shao-Hua Fan, Qian Wang, Xiao-Hong Shu, Qing-You Kong, Xiao-Yan Chen, Jia Liu
JournalJournal of neuro-oncology (J Neurooncol) Vol. 104 Issue 1 Pg. 169-77 (Aug 2011) ISSN: 1573-7373 [Electronic] United States
PMID21161674 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anticarcinogenic Agents
  • Lipopolysaccharides
  • NF-kappa B
  • STAT3 Transcription Factor
  • Stilbenes
  • Tetrazolium Salts
  • Thiazoles
  • Thiocarbamates
  • prolinedithiocarbamate
  • Proline
  • thiazolyl blue
  • Resveratrol
Topics
  • Anticarcinogenic Agents (pharmacology)
  • Apoptosis (drug effects)
  • Cell Line, Tumor
  • Cerebellum (cytology, metabolism)
  • Flow Cytometry
  • Humans
  • Lipopolysaccharides (pharmacology)
  • Medulloblastoma (pathology)
  • NF-kappa B (metabolism)
  • Neurons (metabolism)
  • Proline (analogs & derivatives, pharmacology)
  • Protein Array Analysis
  • Resveratrol
  • STAT3 Transcription Factor (genetics, metabolism)
  • Signal Transduction (drug effects)
  • Stilbenes (pharmacology)
  • Tetrazolium Salts
  • Thiazoles
  • Thiocarbamates (pharmacology)
  • Time Factors

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: