celastrol attenuates the invasion and migration and augments the anticancer effects of bortezomib in a xenograft mouse model of multiple myeloma
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ID: 153065
2018
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Abstract
Several lines of evidence have demonstrated that deregulated activation of NF-κB 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-κB 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-κB 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-α 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.
| Reference Key |
shanmugam2018frontierscelastrol
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| Authors | ;Muthu K. Shanmugam;Kwang S. Ahn;Jong H. Lee;Radhamani Kannaiyan;Nurulhuda Mustafa;Kanjoormana A. Manu;Kodappully S. Siveen;Gautam Sethi;Wee J. Chng;Wee J. Chng;Alan P. Kumar;Alan P. Kumar;Alan P. Kumar;Alan P. Kumar;Alan P. Kumar |
| Journal | chemical research in chinese universities |
| Year | 2018 |
| DOI |
10.3389/fphar.2018.00365
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| URL | |
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