Azidothymidine is effective against human multiple myeloma

dc.contributor.authorPEREIRA, JULIANApt_BR
dc.contributor.authorLEVY, DEBORApt_BR
dc.contributor.authorRUIZ, JORGE L.M.pt_BR
dc.contributor.authorBROCARDO, GRACIELA A.pt_BR
dc.contributor.authorFERREIRA, KLEBER A.pt_BR
dc.contributor.authorCOSTA, RENATA O.pt_BR
dc.contributor.authorQUEIROZ, RODRIGO G.pt_BR
dc.contributor.authorMARIA, DURVANEI A.pt_BR
dc.contributor.authorHALLACK NETO, ABRAHÃO E.pt_BR
dc.contributor.authorCHAMONE, DALTON A.F.pt_BR
dc.contributor.authorBYDLOWSKI, SÉRGIO P.pt_BR
dc.coverageInternacionalpt_BR
dc.date.accessioned2014-07-31T11:35:55Zpt_BR
dc.date.accessioned2014-07-31T11:52:54Z
dc.date.available2014-07-31T11:35:55Zpt_BR
dc.date.available2014-07-31T11:52:54Z
dc.date.issued2013pt_BR
dc.description.abstractAzidothymidine (AZT) is an antiretroviral drug that affects cell proliferation, apoptosis, and the NF-κB pathway. As multiple myeloma (MM) presents with constitutive activation of NF-κB, we analyzed the effect of AZT on human MM cell lines. We evaluated the cytotoxic effect of AZT in human MM cell lines sensitive (8226/S) or resistant to doxorubicin (8226/DX5) and human T cell lymphoblast-like cells, uterine sarcoma cells, and HUVEC using MTT assay. Cytotoxicity was also evaluated in vivo in nude mice xenografted with 8226/S tumor. The effect of AZT on the expression of genes involved in cell proliferation, apoptosis, angiogenesis, and the NF-κB pathway was analyzed in the xenografts using real-time polymerase chain reaction. AZT was effective against both 8226/S and 8226/DX5 cells in a dose and time-dependent manner (p = 0.02) in vitro and promoted cell cycle arrest in S phase in these cells. The tumor volume was lower in mice treated with AZT compared to untreated mice (p = 0.0003). AZT down-regulated the pro-proliferative genes encoding AKT1, MYC, STAT1, MAPK8, MAPK9, CCL-3, Bcl-3, and cyclin D2; pro-angiogenenic genes encoding VEGF and IL8; and genes involved in cell adhesion (ICAM1 and FN1) and the NF-κB pathway. AZT up-regulated the expression of tumor suppressor gene FOXP1 and the pro-apoptotic genes encoding BID, Bcl-10, and caspase-8. Thus, we demonstrated the cytotoxic effect of AZT in human MM cell lines for the first time. Our data may provide the rationale for future clinical trials of AZT for treating MM.
dc.format.extent186-192pt_BR
dc.identifier.citationPEREIRA, JULIANA; LEVY, DEBORA; RUIZ, JORGE L.M.; BROCARDO, GRACIELA A.; FERREIRA, KLEBER A.; COSTA, RENATA O.; QUEIROZ, RODRIGO G.; MARIA, DURVANEI A.; HALLACK NETO, ABRAHÃO E.; CHAMONE, DALTON A.F.; BYDLOWSKI, SÉRGIO P. Azidothymidine is effective against human multiple myeloma: a new use for an old drug?. <b>Anti-Cancer Agents in Medicinal Chemistry</b>, v. 13, n. 1, p. 186-192, 2013. DOI: <a href="https://dx.doi.org/10.2174/187152013804487416">10.2174/187152013804487416</a>. Disponível em: http://repositorio.ipen.br/handle/123456789/8476.
dc.identifier.doi10.2174/187152013804487416
dc.identifier.fasciculo1pt_BR
dc.identifier.issn1871-5206pt_BR
dc.identifier.urihttp://repositorio.ipen.br/handle/123456789/8476pt_BR
dc.identifier.vol13pt_BR
dc.relation.ispartofAnti-Cancer Agents in Medicinal Chemistrypt_BR
dc.rightsclosedAccessen
dc.subjectneoplasmspt_BR
dc.subjectplasma cellspt_BR
dc.subjecthemic diseasespt_BR
dc.subjectmortalitypt_BR
dc.subjectanti-infective agentspt_BR
dc.subjectviral diseasespt_BR
dc.subjectcell proliferationpt_BR
dc.subjectapoptosispt_BR
dc.subjectangiogenesispt_BR
dc.subjecttoxicitypt_BR
dc.titleAzidothymidine is effective against human multiple myelomapt_BR
dc.typeArtigo de periódicopt_BR
dspace.entity.typePublication
ipen.autorDURVANEI AUGUSTO MARIA
ipen.autorRODRIGO GUIMARÃES QUEIROZ
ipen.codigoautor12160
ipen.codigoautor6931
ipen.contributor.ipenauthorDURVANEI AUGUSTO MARIA
ipen.contributor.ipenauthorRODRIGO GUIMARÃES QUEIROZ
ipen.date.recebimento13-12pt_BR
ipen.identifier.fi2.939pt_BR
ipen.identifier.ipendoc19519pt_BR
ipen.identifier.iwosWoSpt_BR
ipen.identifier.ods3
ipen.range.fi1.500 - 2.999
ipen.subtituloa new use for an old drug?
ipen.type.genreArtigo
relation.isAuthorOfPublication42c5c181-64cf-4d75-8e17-c2fa548d8b61
relation.isAuthorOfPublication53d3df0d-4e12-4db7-99fa-dd742a7070fe
relation.isAuthorOfPublication.latestForDiscovery53d3df0d-4e12-4db7-99fa-dd742a7070fe
sigepi.autor.atividadePEREIRA, JULIANA:-1:-1:Spt_BR
sigepi.autor.atividadeLEVY, DEBORA:-1:-1:Npt_BR
sigepi.autor.atividadeRUIZ, JORGE L.M.:-1:-1:Npt_BR
sigepi.autor.atividadeBROCARDO, GRACIELA A.:-1:-1:Npt_BR
sigepi.autor.atividadeFERREIRA, KLEBER A.:-1:-1:Npt_BR
sigepi.autor.atividadeCOSTA, RENATA O.:-1:-1:Npt_BR
sigepi.autor.atividadeQUEIROZ, RODRIGO G.:6931:-1:Npt_BR
sigepi.autor.atividadeMARIA, DURVANEI A.:12160:-1:Npt_BR
sigepi.autor.atividadeHALLACK NETO, ABRAHÃO E.:-1:-1:Npt_BR
sigepi.autor.atividadeCHAMONE, DALTON A.F.:-1:-1:Npt_BR
sigepi.autor.atividadeBYDLOWSKI, SÉRGIO P.:-1:-1:Npt_BR
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