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 language | English (US) |
|---|---|
| Pages (from-to) | 282-290 |
| Number of pages | 9 |
| Journal | Surgery |
| Volume | 146 |
| Issue number | 2 |
| DOIs | |
| State | Published - Aug 1 2009 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Surgery
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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 journal › Article
}
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 -