Celastrol attenuates the invasion and migration and augments the anticancer effects of bortezomib in a xenograft mouse model of multiple myeloma
© 2018 Shanmugam, Ahn, Lee, Kannaiyan, Mustafa, Manu, Siveen, Sethi, Chng and Kumar. 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 molec...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal Article |
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2018
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| Online Access: | http://hdl.handle.net/20.500.11937/69123 |
| _version_ | 1848761973883273216 |
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| author | Shanmugam, M. Ahn, K. Lee, J. Kannaiyan, R. Mustafa, N. Manu, K. Siveen, K. Sethi, G. Chng, W. Kumar, Alan Prem |
| author_facet | Shanmugam, M. Ahn, K. Lee, J. Kannaiyan, R. Mustafa, N. Manu, K. Siveen, K. Sethi, G. Chng, W. Kumar, Alan Prem |
| author_sort | Shanmugam, M. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | © 2018 Shanmugam, Ahn, Lee, Kannaiyan, Mustafa, Manu, Siveen, Sethi, Chng and Kumar. 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-a 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. |
| first_indexed | 2025-11-14T10:40:11Z |
| format | Journal Article |
| id | curtin-20.500.11937-69123 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T10:40:11Z |
| publishDate | 2018 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-691232018-06-29T12:35:25Z Celastrol attenuates the invasion and migration and augments the anticancer effects of bortezomib in a xenograft mouse model of multiple myeloma Shanmugam, M. Ahn, K. Lee, J. Kannaiyan, R. Mustafa, N. Manu, K. Siveen, K. Sethi, G. Chng, W. Kumar, Alan Prem © 2018 Shanmugam, Ahn, Lee, Kannaiyan, Mustafa, Manu, Siveen, Sethi, Chng and Kumar. 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-a 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 Journal Article http://hdl.handle.net/20.500.11937/69123 10.3389/fphar.2018.00365 restricted |
| spellingShingle | Shanmugam, M. Ahn, K. Lee, J. Kannaiyan, R. Mustafa, N. Manu, K. Siveen, K. Sethi, G. Chng, W. Kumar, Alan Prem Celastrol attenuates the invasion and migration and augments the anticancer effects of bortezomib in a xenograft mouse model of multiple myeloma |
| title | Celastrol attenuates the invasion and migration and augments the anticancer effects of bortezomib in a xenograft mouse model of multiple myeloma |
| title_full | Celastrol attenuates the invasion and migration and augments the anticancer effects of bortezomib in a xenograft mouse model of multiple myeloma |
| title_fullStr | Celastrol attenuates the invasion and migration and augments the anticancer effects of bortezomib in a xenograft mouse model of multiple myeloma |
| title_full_unstemmed | Celastrol attenuates the invasion and migration and augments the anticancer effects of bortezomib in a xenograft mouse model of multiple myeloma |
| title_short | Celastrol attenuates the invasion and migration and augments the anticancer effects of bortezomib in a xenograft mouse model of multiple myeloma |
| title_sort | celastrol attenuates the invasion and migration and augments the anticancer effects of bortezomib in a xenograft mouse model of multiple myeloma |
| url | http://hdl.handle.net/20.500.11937/69123 |