Please use this identifier to cite or link to this item: https://doi.org/10.3389/fphar.2018.00365
Title: Celastrol attenuates the invasion and migration and augments the anticancer effects of bortezomib in a xenograft mouse model of multiple myeloma
Authors: Shanmugam, M.K 
Ahn, K.S
Lee, J.H
Kannaiyan, R
Mustafa, N 
Manu, K.A 
Siveen, K.S 
Sethi, G 
Chng, W.J 
Kumar, A.P 
Keywords: bortezomib
caspase 3
celastrol
chemokine receptor CXCR4
gelatinase B
immunoglobulin enhancer binding protein
interleukin 6
syndecan 1
tumor necrosis factor
animal cell
animal experiment
animal model
animal tissue
antineoplastic activity
apoptosis
Article
cell invasion
cell migration
cell proliferation
controlled study
CXCR4 gene
drug effect
drug structure
enzyme activation
enzyme repression
gene product
human
human cell
human tissue
in vitro study
in vivo study
male
MMP 9 gene
mouse
multiple myeloma
nonhuman
protein blood level
protein expression
tumor growth
tumor xenograft
upregulation
Issue Date: 2018
Citation: Shanmugam, M.K, Ahn, K.S, Lee, J.H, Kannaiyan, R, Mustafa, N, Manu, K.A, Siveen, K.S, Sethi, G, Chng, W.J, Kumar, A.P (2018). Celastrol attenuates the invasion and migration and augments the anticancer effects of bortezomib in a xenograft mouse model of multiple myeloma. Frontiers in Pharmacology 9 (MAY) : 365. ScholarBank@NUS Repository. https://doi.org/10.3389/fphar.2018.00365
Abstract: Several lines of evidence have demonstrated that deregulated activation of NF-?B plays a pivotal role in the initiation and progression of a variety of cancers including multiple myeloma (MM). Therefore, novel molecules that can effectively suppress deregulated NF-?B upregulation can potentially reduce MM growth. In this study, the effect of celastrol (CSL) on patient derived CD138+ MM cell proliferation, apoptosis, cell invasion, and migration was investigated. In addition, we studied whether CSL can potentiate the apoptotic effect of bortezomib, a proteasome inhibitor in MM cells and in a xenograft mouse model. We found that CSL significantly reduced cell proliferation and enhanced apoptosis when used in combination with bortezomib and upregulated caspase-3 in these cells. CSL also inhibited invasion and migration of MM cells through the suppression of constitutive NF-?B activation and expression of downstream gene products such as CXCR4 and MMP-9. Moreover, CSL when administered either alone or in combination with bortezomib inhibited MM tumor growth and decreased serum IL-6 and TNF-? levels. Overall, our results suggest that CSL can abrogate MM growth both in vitro and in vivo and may serve as a useful pharmacological agent for the treatment of myeloma and other hematological malignancies. © 2018 Shanmugam, Ahn, Lee, Kannaiyan, Mustafa, Manu, Siveen, Sethi, Chng and Kumar.
Source Title: Frontiers in Pharmacology
URI: https://scholarbank.nus.edu.sg/handle/10635/175386
ISSN: 1663-9812
DOI: 10.3389/fphar.2018.00365
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