Please use this identifier to cite or link to this item: https://doi.org/10.1111/j.1476-5381.2011.01449.x
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dc.titleCelastrol inhibits proliferation and induces chemosensitization through down-regulation of NF-κB and STAT3 regulated gene products in multiple myeloma cells
dc.contributor.authorKannaiyan, R.
dc.contributor.authorHay, H.S.
dc.contributor.authorRajendran, P.
dc.contributor.authorLi, F.
dc.contributor.authorShanmugam, M.K.
dc.contributor.authorVali, S.
dc.contributor.authorAbbasi, T.
dc.contributor.authorKapoor, S.
dc.contributor.authorSharma, A.
dc.contributor.authorKumar, A.P.
dc.contributor.authorChng, W.-J.
dc.contributor.authorSethi, G.
dc.date.accessioned2014-11-25T09:44:14Z
dc.date.available2014-11-25T09:44:14Z
dc.date.issued2011-11
dc.identifier.citationKannaiyan, R., Hay, H.S., Rajendran, P., Li, F., Shanmugam, M.K., Vali, S., Abbasi, T., Kapoor, S., Sharma, A., Kumar, A.P., Chng, W.-J., Sethi, G. (2011-11). Celastrol inhibits proliferation and induces chemosensitization through down-regulation of NF-κB and STAT3 regulated gene products in multiple myeloma cells. British Journal of Pharmacology 164 (5) : 1506-1521. ScholarBank@NUS Repository. https://doi.org/10.1111/j.1476-5381.2011.01449.x
dc.identifier.issn00071188
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/108287
dc.description.abstractBackground and Purpose Activation of pro-inflammatory transcription factors NF-κB and signal transducer and activator of transcription 3 (STAT3) is one of the major contributors to both pathogenesis and chemoresistance in multiple myeloma (MM), which results in high mortality rate. Thus, in the present study, we investigated whether celastrol could suppress the proliferation and induce chemosensitization of MM cells by interfering with NF-κB and STAT3 activation pathways. Experimental Approach The effects of celastrol were investigated using both a virtual predictive tumour cell system and different MM cell lines resistant to doxorubicin, melphalan and bortezomib. Key Results Celastrol inhibited the proliferation of MM cell lines regardless of whether they were sensitive or resistant to bortezomib and other conventional chemotherapeutic drugs. It also synergistically enhanced the apoptotic effects of thalidomide and bortezomib. This correlated with the down-regulation of various proliferative and anti-apoptotic gene products including cyclin D1, Bcl-2, Bcl-xL, survivin, XIAP and Mcl-1. These effects of celastrol were mediated through suppression of constitutively active NF-κB induced by inhibition of IκBα kinase activation; and the phosphorylation of IκBα and of p65. Celastrol also inhibited both the constitutive and IL6-induced activation of STAT3, which induced apoptosis as indicated by an increase in the accumulation of cells in the sub-G1 phase, an increase in the expression of pro-apoptotic proteins and activation of caspase-3. ConclusionS and Implications Thus, based on our experimental findings, we conclude that celastrol may have great potential as a treatment for MM and other haematological malignancies. © 2011 The British Pharmacological Society.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1111/j.1476-5381.2011.01449.x
dc.sourceScopus
dc.subjectcelastrol
dc.subjectmultiple myeloma
dc.subjectNF-κB
dc.subjectSTAT3
dc.typeArticle
dc.contributor.departmentCANCER SCIENCE INSTITUTE OF SINGAPORE
dc.contributor.departmentPHYSIOLOGY
dc.contributor.departmentPHARMACOLOGY
dc.description.doi10.1111/j.1476-5381.2011.01449.x
dc.description.sourcetitleBritish Journal of Pharmacology
dc.description.volume164
dc.description.issue5
dc.description.page1506-1521
dc.description.codenBJPCB
dc.identifier.isiut000296472300012
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