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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP-
dc.contributor.authorPEREIRA, Juliana-
dc.contributor.authorLEVY, Debora-
dc.contributor.authorRUIZ, Jorge L. M.-
dc.contributor.authorBROCARDO, Graciela A.-
dc.contributor.authorFERREIRA, Kleber A.-
dc.contributor.authorCOSTA, Renata O.-
dc.contributor.authorQUEIROZ, Rodrigo G.-
dc.contributor.authorMARIA, Durvanei A.-
dc.contributor.authorHALLACK NETO, Abrahao E.-
dc.contributor.authorCHAMONE, Dalton A. F.-
dc.contributor.authorBYDLOWSKI, Sergio P.-
dc.date.accessioned2014-01-28T22:17:24Z-
dc.date.available2014-01-28T22:17:24Z-
dc.date.issued2013-
dc.identifier.citationANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY, v.13, n.1, p.186-192, 2013-
dc.identifier.issn1871-5206-
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/3935-
dc.description.abstractAzidothymidine (AZT) is an antiretroviral drug that affects cell proliferation, apoptosis, and the NF-kappa B pathway. As multiple myeloma (MM) presents with constitutive activation of NF-kappa B, 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-kappa B 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-kappa B 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.language.isoeng-
dc.publisherBENTHAM SCIENCE PUBL LTD-
dc.relation.ispartofAnti-Cancer Agents in Medicinal Chemistry-
dc.rightsrestrictedAccess-
dc.subjectMultiple myeloma-
dc.subjectZidovudine-
dc.subjectCell proliferation-
dc.subjectApoptosis-
dc.subjectAngiogenesis-
dc.subjectCytotoxic-
dc.subject.othernf-kappa-b-
dc.subject.otherinduced apoptosis-
dc.subject.othercell-line-
dc.subject.othergrowth-
dc.subject.otherexpression-
dc.subject.otherinhibitors-
dc.subject.othercancer-
dc.subject.othertime-
dc.titleAzidothymidine is Effective Against Human Multiple Myeloma: A New Use for an Old Drug?-
dc.typearticle-
dc.rights.holderCopyright BENTHAM SCIENCE PUBL LTD-
dc.identifier.doi10.2174/187152013804487416-
dc.identifier.pmid22931421-
dc.subject.wosOncology-
dc.subject.wosChemistry, Medicinal-
dc.type.categoryoriginal article-
dc.type.versionpublishedVersion-
hcfmusp.author.externalRUIZ, Jorge L. M.:Univ Sao Paulo, Sch Med, Lab Genet & Mol Hematol, LIM 31, Sao Paulo, Brazil-
hcfmusp.author.externalFERREIRA, Kleber A.:Inst Butantan, Sao Paulo, Brazil-
hcfmusp.author.externalCOSTA, Renata O.:Lusiadas Univ, Sch Med, Dept Internal Med, Santos, Brazil-
hcfmusp.author.externalQUEIROZ, Rodrigo G.:Energet & Nucl Res Inst IPEN, Sao Paulo, Brazil-
hcfmusp.author.externalMARIA, Durvanei A.:Inst Butantan, Sao Paulo, Brazil-
hcfmusp.author.externalHALLACK NETO, Abrahao E.:Univ Fed Juiz de Fora, Sch Med, Dept Internal Med, Juiz De Fora, Brazil-
hcfmusp.description.beginpage186-
hcfmusp.description.endpage192-
hcfmusp.description.issue1-
hcfmusp.description.volume2013-
hcfmusp.origemWOS-
hcfmusp.origem.idWOS:000322972400020-
hcfmusp.origem.id2-s2.0-84880163618-
hcfmusp.publisher.citySHARJAH-
hcfmusp.publisher.countryU ARAB EMIRATES-
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dc.description.indexMEDLINE-
hcfmusp.citation.scopus10-
hcfmusp.scopus.lastupdate2022-07-01-
Appears in Collections:

Artigos e Materiais de Revistas Científicas - FM/MCM
Departamento de Clínica Médica - FM/MCM

Artigos e Materiais de Revistas Científicas - HC/ICHC
Instituto Central - HC/ICHC

Artigos e Materiais de Revistas Científicas - HC/InCor
Instituto do Coração - HC/InCor

Artigos e Materiais de Revistas Científicas - LIM/31
LIM/31 - Laboratório de Genética e Hematologia Molecular

Artigos e Materiais de Revistas Científicas - ODS/03
ODS/03 - Saúde e bem-estar


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