Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0021583
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dc.titleDeterminants of sensitivity to DZNep induced Apoptosis in multiple myeloma cells
dc.contributor.authorXie, Z.
dc.contributor.authorBi, C.
dc.contributor.authorCheong, L.L.
dc.contributor.authorLiu, S.C.
dc.contributor.authorHuang, G.
dc.contributor.authorZhou, J.
dc.contributor.authorYu, Q.
dc.contributor.authorChen, C.-S.
dc.contributor.authorChng, W.J.
dc.date.accessioned2014-12-12T07:59:53Z
dc.date.available2014-12-12T07:59:53Z
dc.date.issued2011
dc.identifier.citationXie, Z., Bi, C., Cheong, L.L., Liu, S.C., Huang, G., Zhou, J., Yu, Q., Chen, C.-S., Chng, W.J. (2011). Determinants of sensitivity to DZNep induced Apoptosis in multiple myeloma cells. PLoS ONE 6 (6) : -. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0021583
dc.identifier.issn19326203
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/116973
dc.description.abstractThe 3-Deazaneplanocin A (DZNep), one of S-adenosylhomocysteine (AdoHcy) hydrolase inhibitors, has shown antitumor activities in a broad range of solid tumors and acute myeloid leukemia. Here, we examined its effects on multiple myeloma (MM) cells and found that, at 500 nM, it potently inhibited growth and induced apoptosis in 2 of 8 MM cell lines. RNA from un-treated and DZNep treated cells was profiled by Affymetrix HG-U133 Plus 2.0 microarray and genes with a significant change in gene expression were determined by significance analysis of microarray (SAM) testing. ALOX5 was the most down-regulated gene (5.8-fold) in sensitive cells and was expressed at low level in resistant cells. The results were corroborated by quantitative RT-PCR. Western-blot analysis indicated ALOX5 was highly expressed only in sensitive cell line H929 and greatly decreased upon DZNep treatment. Ectopic expression of ALOX5 reduced sensitivity to DZNep in H929 cells. Furthermore, down-regulation of ALOX5 by RNA interference could also induce apoptosis in H929. Gene expression analysis on MM patient dataset indicated ALOX5 expression was significantly higher in MM patients compared to normal plasma cells. We also found that Bcl-2 was overexpressed in DZNep insensitive cells, and cotreatment with DZNep and ABT-737, a Bcl-2 family inhibitor, synergistically inhibited growth and induced apoptosis of DZNep insensitive MM cells. Taken together, this study shows one of mechanisms of the DZNep efficacy on MM correlates with its ability to down-regulate the ALOX5 levels. In addition, DZNep insensitivity might be associated with overexpression of Bcl-2, and the combination of ABT-737 and DZNep could synergistically induced apoptosis. These results suggest that DZNep may be exploited therapeutically for a subset of MM. © 2011 Xie et al.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1371/journal.pone.0021583
dc.sourceScopus
dc.typeArticle
dc.contributor.departmentCANCER SCIENCE INSTITUTE OF SINGAPORE
dc.description.doi10.1371/journal.pone.0021583
dc.description.sourcetitlePLoS ONE
dc.description.volume6
dc.description.issue6
dc.description.page-
dc.identifier.isiut000292036900057
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