Triptolide therapy for neuroblastoma decreases cell viability in vitro and inhibits tumor growth in vivo

Mara B. Antonoff*, Rohit Chugh, Daniel Borja-Cacho, Vikas Dudeja, Kimberly A. Clawson, Steven J. Skube, Brent S. Sorenson, Daniel A. Saltzman, Selwyn M. Vickers, Ashok K. Saluja

*Corresponding author for this work

Research output: Contribution to journalArticle

68 Scopus citations

Abstract

Background: Heat shock protein (Hsp)-70 is overexpressed in several human malignancies, and its inhibition has been shown to kill cancer cells. Our objectives were to assess the effectiveness of triptolide, an Hsp-70 inhibitor, in treating neuroblastoma in vitro and in vivo, and to measure the associated effects on Hsp-70 levels and apoptosis markers. Methods: After exposing N2a and SKNSH cell lines to triptolide, cell viability was assessed. Caspase-3 and -9 activities were measured and annexin staining performed to determine if cell death occurred via apoptosis. Hsp-70 protein and mRNA levels were determined using Western blot and real-time polymerase chain reaction. In an orthotopic tumor model, mice received daily triptolide injections and were humanely killed at study completion with tumor measurement. Results: Triptolide treatment resulted in dose- and time-dependent N2a cell death and dose-dependent SKNSH killing. Triptolide exposure was associated with dose-dependent increases in caspase activity and annexin staining. Triptolide decreased Hsp-70 protein and mRNA levels in a dose-dependent fashion. Mice receiving triptolide therapy had significantly smaller tumors than controls. Conclusion: Triptolide therapy decreased neuroblastoma cell viability in vitro and inhibited tumor growth in vivo. Our studies suggest that triptolide killed cells via apoptosis and in association with inhibition of Hsp-70 expression. Triptolide may provide a novel therapy for neuroblastoma.

Original languageEnglish (US)
Pages (from-to)282-290
Number of pages9
JournalSurgery
Volume146
Issue number2
DOIs
StatePublished - Aug 1 2009

ASJC Scopus subject areas

  • Surgery

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