Organopalladium compound 7b targets mitochondrial thiols and induces caspase-dependent apoptosis in human myeloid leukemia cells

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dc.contributor.author Moraes, V. W. R.
dc.contributor.author Caires, A. C. F.
dc.contributor.author Paredes-Gamero, Edgar Julian [UNIFESP]
dc.contributor.author Rodrigues, T.
dc.date.accessioned 2016-01-24T14:31:48Z
dc.date.available 2016-01-24T14:31:48Z
dc.date.issued 2013-06-01
dc.identifier http://dx.doi.org/10.1038/cddis.2013.190
dc.identifier.citation Cell Death & Disease. London: Nature Publishing Group, v. 4, 8 p., 2013.
dc.identifier.issn 2041-4889
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/36361
dc.description.abstract The advances in the treatment of chronic myeloid leukemia (CML) during the last years were also accompanied by the development of evading strategies by tumor cells, resulting in chemotherapy resistance in some patients. Patented organopalladium compounds derived from the reaction of N, N-dimethyl-1-phenethylamine (dmpa) with [1,2-ethanebis(diphenylphosphine)] (dppe) exhibited a potent antitumor activity in vivo and in vitro in melanoma cells. We showed here that the cyclopalladated derivative [Pd-2(R(+))C-2, N-dmpa)(2)(mu-dppe) Cl-2], named compound 7b, was highly effective to promote cell death in the K562 human leukemia cells and its mechanisms of action were investigated. It was shown that compound 7b was able to promote exclusively apoptotic cell death in K562 cells associated to cytochrome c release and caspase 3 activation. This cytotoxic effect was not observed in normal peripheral mononuclear blood cells. the compound 7b-induced intrinsic apoptotic pathway was triggered by the protein thiol oxidation that resulted in the dissipation of the mitochondrial transmembrane potential. the preventive effect of the dithiothreitol on the compound 7b-induced cell death and all downstream events associated to apoptosis confirmed that death signal was elicited by the thiol oxidation. These findings contribute to the elucidation of the palladacycle 7b-induced cell death mechanism and present this compound as a promising drug in the CML antitumor chemotherapy. en
dc.description.sponsorship Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorship Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.format.extent 8
dc.language.iso eng
dc.publisher Nature Publishing Group
dc.relation.ispartof Cell Death & Disease
dc.rights Acesso aberto
dc.subject antitumor chemotherapy en
dc.subject apoptosis en
dc.subject K562 cells en
dc.subject leukemia en
dc.subject mitochondrial permeabilization en
dc.subject palladacycle en
dc.title Organopalladium compound 7b targets mitochondrial thiols and induces caspase-dependent apoptosis in human myeloid leukemia cells en
dc.type Artigo
dc.contributor.institution Universidade Federal do ABC (UFABC)
dc.contributor.institution Univ Mogi das Cruzes
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.description.affiliation Univ Fed ABC, Ctr Ciencias Nat & Humanas, BR-09210170 São Paulo, Brazil
dc.description.affiliation Univ Mogi das Cruzes, Ctr Interdisciplinar Invest Bioquim, São Paulo, Brazil
dc.description.affiliation Universidade Federal de São Paulo UNIFESP, Dept Bioquim, São Paulo, Brazil
dc.description.affiliationUnifesp Universidade Federal de São Paulo UNIFESP, Dept Bioquim, São Paulo, Brazil
dc.description.sponsorshipID FAPESP: 2012/12247-8
dc.description.sponsorshipID CNPq: 476824/2010-9
dc.identifier.file WOS000321111700009.pdf
dc.identifier.doi 10.1038/cddis.2013.190
dc.description.source Web of Science
dc.identifier.wos WOS:000321111700009



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