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Am J Surg. 2013 Apr;205(4):387-96. doi: 10.1016/j.amjsurg.2013.01.008. Epub 2013 Feb 19.

Triptolide-mediated cell death in neuroblastoma occurs by both apoptosis and autophagy pathways and results in inhibition of nuclear factor-kappa B activity.

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1
Department of Surgery, University of Minnesota, 420 Delaware Street SE, Mayo Mail Code 195, Minneapolis, MN 55455, USA. kend0057@umn.edu

Abstract

BACKGROUND:

Neuroblastoma is an aggressive pediatric malignancy with significant chemotherapeutic resistance. We assessed triptolide as a potential therapy.

METHODS:

SH-SY5Y and IMR-32 neuroblastoma cell lines were treated with triptolide. Viability, intracellular calcium, caspase activation, protein, and mRNA levels were measured. Autophagy was evaluated with confocal microscopy. Nuclear factor-kappa B (NF-κB) activation was measured using a dual luciferase assay.

RESULTS:

Triptolide treatment resulted in death in both cell lines within 72 hours, with sustained increases in intracellular calcium. IMR-32 cells underwent cell death by apoptosis. Conversely, light chain 3II (LC3II) protein levels were elevated in SH-SY5Y cells, which is consistent with autophagy. Confocal microscopy confirmed increased LC3 puncta in SH-SY5Y cells compared with control cells. Heat shock pathway protein and mRNA levels decreased with treatment. NF-κB assays demonstrated inhibition of tumor necrosis factor (TNF)-α-induced activity with triptolide.

CONCLUSIONS:

Triptolide treatment induces cell death in neuroblastoma by different mechanisms with multiple pathways targeted. Triptolide may serve a potential chemotherapeutic role in advanced cases of neuroblastoma.

PMID:
23428154
DOI:
10.1016/j.amjsurg.2013.01.008
[Indexed for MEDLINE]
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