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 Saluja

Research output: Contribution to journalArticle

64 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Neuroblastoma
Cell Survival
HSP70 Heat-Shock Proteins
Growth
Neoplasms
Annexins
Therapeutics
Apoptosis
Cell Death
triptolide
In Vitro Techniques
Staining and Labeling
Messenger RNA
Caspase 9
Caspases
Caspase 3
Real-Time Polymerase Chain Reaction
Proteins
Western Blotting
Cell Line

ASJC Scopus subject areas

  • Surgery

Cite this

Triptolide therapy for neuroblastoma decreases cell viability in vitro and inhibits tumor growth in vivo. / Antonoff, Mara B.; Chugh, Rohit; Borja-Cacho, Daniel; Dudeja, Vikas; Clawson, Kimberly A.; Skube, Steven J.; Sorenson, Brent S.; Saltzman, Daniel A.; Vickers, Selwyn M.; Saluja, Ashok.

In: Surgery, Vol. 146, No. 2, 01.08.2009, p. 282-290.

Research output: Contribution to journalArticle

Antonoff, MB, Chugh, R, Borja-Cacho, D, Dudeja, V, Clawson, KA, Skube, SJ, Sorenson, BS, Saltzman, DA, Vickers, SM & Saluja, A 2009, 'Triptolide therapy for neuroblastoma decreases cell viability in vitro and inhibits tumor growth in vivo', Surgery, vol. 146, no. 2, pp. 282-290. https://doi.org/10.1016/j.surg.2009.04.023
Antonoff, Mara B. ; Chugh, Rohit ; Borja-Cacho, Daniel ; Dudeja, Vikas ; Clawson, Kimberly A. ; Skube, Steven J. ; Sorenson, Brent S. ; Saltzman, Daniel A. ; Vickers, Selwyn M. ; Saluja, Ashok. / Triptolide therapy for neuroblastoma decreases cell viability in vitro and inhibits tumor growth in vivo. In: Surgery. 2009 ; Vol. 146, No. 2. pp. 282-290.
@article{206e553640044d2b90c0517c78d1461e,
title = "Triptolide therapy for neuroblastoma decreases cell viability in vitro and inhibits tumor growth in vivo",
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.",
author = "Antonoff, {Mara B.} and Rohit Chugh and Daniel Borja-Cacho and Vikas Dudeja and Clawson, {Kimberly A.} and Skube, {Steven J.} and Sorenson, {Brent S.} and Saltzman, {Daniel A.} and Vickers, {Selwyn M.} and Ashok Saluja",
year = "2009",
month = "8",
day = "1",
doi = "10.1016/j.surg.2009.04.023",
language = "English (US)",
volume = "146",
pages = "282--290",
journal = "Surgery (United States)",
issn = "0039-6060",
publisher = "Mosby Inc.",
number = "2",

}

TY - JOUR

T1 - Triptolide therapy for neuroblastoma decreases cell viability in vitro and inhibits tumor growth in vivo

AU - Antonoff, Mara B.

AU - Chugh, Rohit

AU - Borja-Cacho, Daniel

AU - Dudeja, Vikas

AU - Clawson, Kimberly A.

AU - Skube, Steven J.

AU - Sorenson, Brent S.

AU - Saltzman, Daniel A.

AU - Vickers, Selwyn M.

AU - Saluja, Ashok

PY - 2009/8/1

Y1 - 2009/8/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=67650552674&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67650552674&partnerID=8YFLogxK

U2 - 10.1016/j.surg.2009.04.023

DO - 10.1016/j.surg.2009.04.023

M3 - Article

C2 - 19628086

AN - SCOPUS:67650552674

VL - 146

SP - 282

EP - 290

JO - Surgery (United States)

JF - Surgery (United States)

SN - 0039-6060

IS - 2

ER -