SB225002 induces cell death and cell cycle arrest in acute lymphoblastic leukemia cells through the activation of GLIPR1

 

Show simple item record

dc.contributor.author De Vasconcellos, Jaíra Ferreira en_ZA
dc.contributor.author Laranjeira, Angelo Brunelli Albertoni en_ZA
dc.contributor.author Leal, Paulo C en_ZA
dc.contributor.author Bhasin, Manoj K en_ZA
dc.contributor.author Zenatti, Priscila Pini en_ZA
dc.contributor.author Nunes, Ricardo J en_ZA
dc.contributor.author Yunes, Rosendo A en_ZA
dc.contributor.author Nowill, Alexandre E en_ZA
dc.contributor.author Libermann, Towia A en_ZA
dc.contributor.author Zerbini, Luiz Fernando en_ZA
dc.contributor.author Yunes, José Andrés en_ZA
dc.date.accessioned 2016-02-10T14:47:18Z
dc.date.available 2016-02-10T14:47:18Z
dc.date.issued 2015 en_ZA
dc.identifier.citation de Vasconcellos, J. F., Laranjeira, A. B., Leal, P. C., Bhasin, M. K., Zenatti, P. P., Nunes, R. J., ... & Yunes, J. A. (2014) .SB225002 induces cell death and cell cycle arrest in acute lymphoblastic leukemia cells through the activation of GLIPR1. PloS one, 10(8), e0134783-e0134783. doi:10.1371/journal.pone.0134783 en_ZA
dc.identifier.uri http://dx.doi.org/10.1371/journal.pone.0134783 en_ZA
dc.identifier.uri http://hdl.handle.net/11427/16953
dc.description.abstract Acute Lymphoblastic Leukemia (ALL) is the most frequent childhood malignancy. In the effort to find new anti-leukemic agents, we evaluated the small drug SB225002 (N-(2-hydroxy-4-nitrophenyl)-N'-(2-bromophenyl)urea). Although initially described as a selective antagonist of CXCR2, later studies have identified other cellular targets for SB225002, with potential medicinal use in cancer. We found that SB225002 has a significant pro-apoptotic effect against both B- and T-ALL cell lines. Cell cycle analysis demonstrated that treatment with SB225002 induces G2-M cell cycle arrest. Transcriptional profiling revealed that SB225002-mediated apoptosis triggered a transcriptional program typical of tubulin binding agents. Network analysis revealed the activation of genes linked to the JUN and p53 pathways and inhibition of genes linked to the TNF pathway. Early cellular effects activated by SB225002 included the up-regulation of GLIPR1 , a p53-target gene shown to have pro-apoptotic activities in prostate and bladder cancer. Silencing of GLIPR1 in B- and T-ALL cell lines resulted in increased resistance to SB225002. Although SB225002 promoted ROS increase in ALL cells, antioxidant N-Acetyl Cysteine pre-treatment only modestly attenuated cell death, implying that the pro-apoptotic effects of SB225002 are not exclusively mediated by ROS. Moreover, GLIPR1 silencing resulted in increased ROS levels both in untreated and SB225002-treated cells. In conclusion, SB225002 induces cell cycle arrest and apoptosis in different B- and T-ALL cell lines. Inhibition of tubulin function with concurrent activation of the p53 pathway, in particular, its downstream target GLIPR1 , seems to underlie the anti-leukemic effect of SB225002. en_ZA
dc.language.iso eng en_ZA
dc.publisher Public Library of Science en_ZA
dc.rights 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. en_ZA
dc.rights.uri http://creativecommons.org/licenses/by/4.0 en_ZA
dc.source PLoS One en_ZA
dc.source.uri http://journals.plos.org/plosone en_ZA
dc.subject.other Acute lymphoblastic leukemia en_ZA
dc.subject.other Apoptosis en_ZA
dc.subject.other Cell cycle and cell division en_ZA
dc.subject.other Gene expression en_ZA
dc.subject.other Reactive oxygen species en_ZA
dc.subject.other Tubulins en_ZA
dc.subject.other Lymphocytes en_ZA
dc.subject.other Cloning en_ZA
dc.title SB225002 induces cell death and cell cycle arrest in acute lymphoblastic leukemia cells through the activation of GLIPR1 en_ZA
dc.type Journal Article en_ZA
dc.rights.holder © 2015 de Vasconcellos et al en_ZA
uct.type.publication Research en_ZA
uct.type.resource Article en_ZA
dc.publisher.institution University of Cape Town
dc.publisher.faculty Faculty of Health Sciences en_ZA
dc.publisher.department Division of Medical Biochemistry en_ZA
uct.type.filetype Text
uct.type.filetype Image
dc.identifier.apacitation De Vasconcellos, J. F., Laranjeira, A. B. A., Leal, P. C., Bhasin, M. K., Zenatti, P. P., Nunes, R. J., ... Yunes, J. A. (2015). SB225002 induces cell death and cell cycle arrest in acute lymphoblastic leukemia cells through the activation of GLIPR1. <i>PLoS One</i>, http://hdl.handle.net/11427/16953 en_ZA
dc.identifier.chicagocitation De Vasconcellos, Jaíra Ferreira, Angelo Brunelli Albertoni Laranjeira, Paulo C Leal, Manoj K Bhasin, Priscila Pini Zenatti, Ricardo J Nunes, Rosendo A Yunes, et al "SB225002 induces cell death and cell cycle arrest in acute lymphoblastic leukemia cells through the activation of GLIPR1." <i>PLoS One</i> (2015) http://hdl.handle.net/11427/16953 en_ZA
dc.identifier.vancouvercitation De Vasconcellos JF, Laranjeira ABA, Leal PC, Bhasin MK, Zenatti PP, Nunes RJ, et al. SB225002 induces cell death and cell cycle arrest in acute lymphoblastic leukemia cells through the activation of GLIPR1. PLoS One. 2015; http://hdl.handle.net/11427/16953. en_ZA
dc.identifier.ris TY - Journal Article AU - De Vasconcellos, Jaíra Ferreira AU - Laranjeira, Angelo Brunelli Albertoni AU - Leal, Paulo C AU - Bhasin, Manoj K AU - Zenatti, Priscila Pini AU - Nunes, Ricardo J AU - Yunes, Rosendo A AU - Nowill, Alexandre E AU - Libermann, Towia A AU - Zerbini, Luiz Fernando AU - Yunes, José Andrés AB - Acute Lymphoblastic Leukemia (ALL) is the most frequent childhood malignancy. In the effort to find new anti-leukemic agents, we evaluated the small drug SB225002 (N-(2-hydroxy-4-nitrophenyl)-N'-(2-bromophenyl)urea). Although initially described as a selective antagonist of CXCR2, later studies have identified other cellular targets for SB225002, with potential medicinal use in cancer. We found that SB225002 has a significant pro-apoptotic effect against both B- and T-ALL cell lines. Cell cycle analysis demonstrated that treatment with SB225002 induces G2-M cell cycle arrest. Transcriptional profiling revealed that SB225002-mediated apoptosis triggered a transcriptional program typical of tubulin binding agents. Network analysis revealed the activation of genes linked to the JUN and p53 pathways and inhibition of genes linked to the TNF pathway. Early cellular effects activated by SB225002 included the up-regulation of GLIPR1 , a p53-target gene shown to have pro-apoptotic activities in prostate and bladder cancer. Silencing of GLIPR1 in B- and T-ALL cell lines resulted in increased resistance to SB225002. Although SB225002 promoted ROS increase in ALL cells, antioxidant N-Acetyl Cysteine pre-treatment only modestly attenuated cell death, implying that the pro-apoptotic effects of SB225002 are not exclusively mediated by ROS. Moreover, GLIPR1 silencing resulted in increased ROS levels both in untreated and SB225002-treated cells. In conclusion, SB225002 induces cell cycle arrest and apoptosis in different B- and T-ALL cell lines. Inhibition of tubulin function with concurrent activation of the p53 pathway, in particular, its downstream target GLIPR1 , seems to underlie the anti-leukemic effect of SB225002. DA - 2015 DB - OpenUCT DO - 10.1371/journal.pone.0134783 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2015 T1 - SB225002 induces cell death and cell cycle arrest in acute lymphoblastic leukemia cells through the activation of GLIPR1 TI - SB225002 induces cell death and cell cycle arrest in acute lymphoblastic leukemia cells through the activation of GLIPR1 UR - http://hdl.handle.net/11427/16953 ER - en_ZA


Files in this item

This item appears in the following Collection(s)

Show simple item record

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. Except where otherwise noted, this item's license is described as 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.