Minnelide reduces tumor burden in preclinical models of osteosarcoma

Sulagna Banerjee; Venugopal Thayanithy; Veena Sangwan; Tiffany N. Mackenzie; Ashok K. Saluja; Subbaya Subramanian

doi:10.1016/j.canlet.2013.02.050

Minnelide reduces tumor burden in preclinical models of osteosarcoma

Sulagna Banerjee, Venugopal Thayanithy, Veena Sangwan, Tiffany N. Mackenzie, Ashok K. Saluja, Subbaya Subramanian

Research output: Contribution to journal › Article › peer-review

40 Scopus citations

Abstract

Osteosarcoma is the most common bone cancer in children and adolescents with a 5-year survival rate of about 70%. In this study, we have evaluated the preclinical therapeutic efficacy of the novel synthetic drug, Minnelide, a prodrug of triptolide on osteosarcoma. Triptolide was effective in significantly inducing apoptosis in all osteosarcoma cell lines tested but had no significant effect on the human osteoblast cells. Notably, Minnelide treatment significantly reduced tumor burden and lung metastasis in the orthotopic and lung colonization models. Triptolide/Minnelide effectively downregulated the levels of pro-survival proteins such as heat shock proteins, cMYC, survivin and targets the NF-κB pathway.

Original language	English (US)
Pages (from-to)	412-420
Number of pages	9
Journal	Cancer letters
Volume	335
Issue number	2
DOIs	https://doi.org/10.1016/j.canlet.2013.02.050
State	Published - Jul 28 2013
Externally published	Yes

Keywords

Heat shock proteins
Minnelide
NF-κB
Osteosarcoma
Triptolide

ASJC Scopus subject areas

Oncology
Cancer Research

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title = "Minnelide reduces tumor burden in preclinical models of osteosarcoma",

abstract = "Osteosarcoma is the most common bone cancer in children and adolescents with a 5-year survival rate of about 70%. In this study, we have evaluated the preclinical therapeutic efficacy of the novel synthetic drug, Minnelide, a prodrug of triptolide on osteosarcoma. Triptolide was effective in significantly inducing apoptosis in all osteosarcoma cell lines tested but had no significant effect on the human osteoblast cells. Notably, Minnelide treatment significantly reduced tumor burden and lung metastasis in the orthotopic and lung colonization models. Triptolide/Minnelide effectively downregulated the levels of pro-survival proteins such as heat shock proteins, cMYC, survivin and targets the NF-κB pathway.",

keywords = "Heat shock proteins, Minnelide, NF-κB, Osteosarcoma, Triptolide",

author = "Sulagna Banerjee and Venugopal Thayanithy and Veena Sangwan and Mackenzie, {Tiffany N.} and Saluja, {Ashok K.} and Subbaya Subramanian",

note = "Funding Information: This study was supported by grants R01CA124723 and R01CA170496 from the NIH (A.K.S.), by a Faculty Research and Development grant from the University of Minnesota Academic Health Center, by a translational research grant from the Masonic Cancer Center, University of Minnesota, by grants from the Wyckoff Rein in Sarcoma (S.S.). Copyright: Copyright 2013 Elsevier B.V., All rights reserved.",

year = "2013",

month = jul,

day = "28",

doi = "10.1016/j.canlet.2013.02.050",

language = "English (US)",

volume = "335",

pages = "412--420",

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AU - Banerjee, Sulagna

AU - Thayanithy, Venugopal

AU - Sangwan, Veena

AU - Mackenzie, Tiffany N.

AU - Saluja, Ashok K.

AU - Subramanian, Subbaya

N1 - Funding Information: This study was supported by grants R01CA124723 and R01CA170496 from the NIH (A.K.S.), by a Faculty Research and Development grant from the University of Minnesota Academic Health Center, by a translational research grant from the Masonic Cancer Center, University of Minnesota, by grants from the Wyckoff Rein in Sarcoma (S.S.). Copyright: Copyright 2013 Elsevier B.V., All rights reserved.

PY - 2013/7/28

Y1 - 2013/7/28

N2 - Osteosarcoma is the most common bone cancer in children and adolescents with a 5-year survival rate of about 70%. In this study, we have evaluated the preclinical therapeutic efficacy of the novel synthetic drug, Minnelide, a prodrug of triptolide on osteosarcoma. Triptolide was effective in significantly inducing apoptosis in all osteosarcoma cell lines tested but had no significant effect on the human osteoblast cells. Notably, Minnelide treatment significantly reduced tumor burden and lung metastasis in the orthotopic and lung colonization models. Triptolide/Minnelide effectively downregulated the levels of pro-survival proteins such as heat shock proteins, cMYC, survivin and targets the NF-κB pathway.

AB - Osteosarcoma is the most common bone cancer in children and adolescents with a 5-year survival rate of about 70%. In this study, we have evaluated the preclinical therapeutic efficacy of the novel synthetic drug, Minnelide, a prodrug of triptolide on osteosarcoma. Triptolide was effective in significantly inducing apoptosis in all osteosarcoma cell lines tested but had no significant effect on the human osteoblast cells. Notably, Minnelide treatment significantly reduced tumor burden and lung metastasis in the orthotopic and lung colonization models. Triptolide/Minnelide effectively downregulated the levels of pro-survival proteins such as heat shock proteins, cMYC, survivin and targets the NF-κB pathway.

KW - Heat shock proteins

KW - Minnelide

KW - NF-κB

KW - Osteosarcoma

KW - Triptolide

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JO - Cancer Letters

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Minnelide reduces tumor burden in preclinical models of osteosarcoma

Abstract

Keywords

ASJC Scopus subject areas

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