Azidothymidine is Effective Against Human Multiple Myeloma: A New Use for an Old Drug?

Página do item simplificado
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.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.description.indexMEDLINE
dc.identifier.citationANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY, v.13, n.1, p.186-192, 2013
dc.identifier.doi10.2174/187152013804487416
dc.identifier.issn1871-5206
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/3935
dc.language.isoeng
dc.publisherBENTHAM SCIENCE PUBL LTD
dc.relation.ispartofAnti-Cancer Agents in Medicinal Chemistry
dc.rightsrestrictedAccess
dc.rights.holderCopyright BENTHAM SCIENCE PUBL LTD
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.subject.wosOncology
dc.subject.wosChemistry, Medicinal
dc.titleAzidothymidine is Effective Against Human Multiple Myeloma: A New Use for an Old Drug?
dc.typearticle
dc.type.categoryoriginal article
dc.type.versionpublishedVersion
dspace.entity.typePublication
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.citation.scopus10
hcfmusp.contributor.author-fmusphcJULIANA PEREIRA
hcfmusp.contributor.author-fmusphcDEBORA LEVY
hcfmusp.contributor.author-fmusphcGRACIELA APARECIDA BROCARDO
hcfmusp.contributor.author-fmusphcDALTON DE ALENCAR FISCHER CHAMONE
hcfmusp.contributor.author-fmusphcSERGIO PAULO BYDLOWSKI
hcfmusp.description.beginpage186
hcfmusp.description.endpage192
hcfmusp.description.issue1
hcfmusp.description.volume2013
hcfmusp.origemWOS
hcfmusp.origem.pubmed22931421
hcfmusp.origem.scopus2-s2.0-84880163618
hcfmusp.origem.wosWOS:000322972400020
hcfmusp.publisher.citySHARJAH
hcfmusp.publisher.countryU ARAB EMIRATES
hcfmusp.relation.referenceBazzi M., 2010, CANCER BIOL THER, V23, P830
hcfmusp.relation.referenceBower M, 1999, AIDS, V13, P2105, DOI 10.1097/00002030-199910220-00014
hcfmusp.relation.referenceChen SH, 2010, ANTICANCER RES, V30, P4177
hcfmusp.relation.referenceChow WA, 2009, LANCET ONCOL, V10, P61, DOI 10.1016/S1470-2045(08)70334-6
hcfmusp.relation.referenceDALTON WS, 1986, CANCER RES, V46, P5125
hcfmusp.relation.referenceFan QW, 2010, SCI SIGNAL, V3, DOI 10.1126/scisignal.2001017
hcfmusp.relation.referenceGhosh SK, 2003, BLOOD, V101, P2321, DOI 10.1182/blood-2002-08-2525
hcfmusp.relation.referenceGyrd-Hansen M, 2010, NAT REV CANCER, V10, P561, DOI 10.1038/nrc2889
hcfmusp.relation.referenceHideshima T, 2001, CANCER RES, V61, P3071
hcfmusp.relation.referenceHumer J, 2008, MELANOMA RES, V18, P314, DOI 10.1097/CMR.0b013e32830aaaa6
hcfmusp.relation.referenceLiu Q, 2003, BLOOD, V101, P4078, DOI 10.1182/blood-2002-10-3231
hcfmusp.relation.referenceLivak KJ, 2001, METHODS, V25, P402, DOI 10.1006/meth.2001.1262
hcfmusp.relation.referenceMITSUYA H, 1985, P NATL ACAD SCI USA, V82, P7096, DOI 10.1073/pnas.82.20.7096
hcfmusp.relation.referenceMOSMANN T, 1983, J IMMUNOL METHODS, V65, P55, DOI 10.1016/0022-1759(83)90303-4
hcfmusp.relation.referenceNakanishi C, 2005, NAT REV CANCER, V5, P297, DOI 10.1038/nrc1588
hcfmusp.relation.referenceSailaja G, 1996, BIOCHEM PHARMACOL, V52, P857, DOI 10.1016/0006-2952(96)82183-6
hcfmusp.relation.referenceSolaini G, 2007, BIOSCIENCE REP, V27, P11, DOI 10.1007/s10540-007-9033-4
hcfmusp.relation.referencevan der Meel R, 2011, DRUG DISCOV TODAY, V16, P219, DOI 10.1016/j.drudis.2011.01.005
hcfmusp.scopus.lastupdate2024-05-10
relation.isAuthorOfPublication58959854-e2e3-4246-9a9e-ca4b771aa16f
relation.isAuthorOfPublication82037efd-05e2-4a33-99b3-6b34a680d053
relation.isAuthorOfPublication090d992f-efb0-4316-81dd-483131e9491a
relation.isAuthorOfPublication8803fb50-ed6d-409b-9826-6a1a3be7b818
relation.isAuthorOfPublication34f28529-437f-4414-8216-701def73f655
relation.isAuthorOfPublication.latestForDiscovery58959854-e2e3-4246-9a9e-ca4b771aa16f
Arquivos
Pacote Original
Agora exibindo 1 - 1 de 1
Nenhuma Miniatura disponível
Nome:
art_PEREIRA_Azidothymidine_is_Effective_Against_Human_Multiple_Myeloma_A_2013.PDF
Tamanho:
247.9 KB
Formato:
Adobe Portable Document Format
Descrição:
publishedVersion (English)
Baixar
Coleções
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - HC/InCor
Artigos e Materiais de Revistas Científicas - LIM/31
Artigos e Materiais de Revistas Científicas - ODS/03