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

Tara C.K. Krosch, Veena Sangwan, Sulagna Banerjee, Nameeta Mujumdar, Vikas Dudeja, Ashok K. Saluja, Selwyn M. Vickers

Research output: Contribution to journalArticle

38 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)387-396
Number of pages10
JournalAmerican journal of surgery
Volume205
Issue number4
DOIs
StatePublished - Apr 1 2013
Externally publishedYes

Keywords

  • Apoptosis
  • Autophagy
  • Heat shock protein
  • NF-κB
  • Neuroblastoma
  • Triptolide

ASJC Scopus subject areas

  • Surgery

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