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dc.contributor.authorDasari, Venkata Ramesh
dc.contributor.authorVelpula, Kiran Kumar
dc.contributor.authorKaur, Kiranpreet
dc.contributor.authorFassett, Daniel
dc.contributor.authorKlopfenstein, Jeffrey D.
dc.contributor.authorDinh, Dzung H.
dc.contributor.authorGujrati, Meena
dc.contributor.authorRao, Jasti S.
dc.date.accessioned2011-05-27T15:27:39Z
dc.date.available2011-05-27T15:27:39Z
dc.date.issued2010-07-28
dc.identifier.bibliographicCitationDasari, V. R., Velpula, K. K., Kaur, K., Fassett, D., Klopfenstein, J. D., Dinh, D. H., Gujrati, M., & Rao, J. S. 2010. Cord blood stem cell-mediated induction of apoptosis in glioma downregulates X-linked inhibitor of apoptosis protein (XIAP). PLoS One, 5(7): e11813. DOI:10.1371/journal.pone.0011813en
dc.identifier.issn1932-6203
dc.identifier.otherDOI:10.1371/journal.pone.0011813
dc.identifier.urihttp://hdl.handle.net/10027/7720
dc.description© 2010 Dasari et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The original source for this publication is at Public Library of Science. DOI:10.1371/journal.pone.0011813en
dc.description.abstractBackground: XIAP (X-linked inhibitor of apoptosis protein) is one of the most important members of the apoptosis inhibitor family. XIAP is upregulated in various malignancies, including human glioblastoma. It promotes invasion, metastasis, growth and survival of malignant cells. We hypothesized that downregulation of XIAP by human umbilical cord blood mesenchymal stem cells (hUCBSC) in glioma cells would cause them to undergo apoptotic death. Methodology/Principal Findings: We observed the effect of hUCBSC on two malignant glioma cell lines (SNB19 and U251) and two glioma xenograft cell lines (4910 and 5310). In co-cultures of glioma cells with hUCBSC, proliferation of glioma cells was significantly inhibited. This is associated with increased cytotoxicity of glioma cells, which led to glioma cell death. Stem cells induced apoptosis in glioma cells, which was evaluated by TUNEL assay, FACS analyses and immunoblotting. The induction of apoptosis is associated with inhibition of XIAP in co-cultures of hUCBSC. Similar results were obtained by the treatment of glioma cells with shRNA to downregulate XIAP (siXIAP). Downregulation of XIAP resulted in activation of caspase-3 and caspase-9 to trigger apoptosis in glioma cells. Apoptosis is characterized by the loss of mitochondrial membrane potential and upregulation of mitochondrial apoptotic proteins Bax and Bad. Cell death of glioma cells was marked by downregulation of Akt and phospho-Akt molecules. We observed similar results under in vivo conditions in U251- and 5310-injected nude mice brains, which were treated with hUCBSC. Under in vivo conditions, Smac/DIABLO was found to be colocalized in the nucleus, showing that hUCBSC induced apoptosis is mediated by inhibition of XIAP and activation of Smac/DIABLO. Conclusions/Significance: Our results indicate that downregulation of XIAP by hUCBSC treatment induces apoptosis, which led to the death of the glioma cells and xenograft cells. This study demonstrates the therapeutic potential of XIAP and hUCBSC to treat malignant gliomas.en
dc.description.sponsorshipThis study was funded by the National Institute of Neurological Disorders and Stroke (NINDS), NS057529.en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.subjectgliomasen
dc.subjectapoptosis proteinen
dc.titleCord Blood Stem Cell-Mediated Induction of Apoptosis in Glioma Downregulates X-Linked Inhibitor of Apoptosis Protein (XIAP)en
dc.typeArticleen


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