Amblyomin-X induces ER stress, mitochondrial dysfunction, and caspase activation in human melanoma and pancreatic tumor cell

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dc.citation.volume415
dc.contributor.authorMorais, Katia Luciano Pereira [UNIFESP]
dc.contributor.authorFernandes Pacheco, Mario Thiego
dc.contributor.authorBerra, Carolina Maria
dc.contributor.authorBosch, Rosemary V.
dc.contributor.authorSciani, Juliana Mozer
dc.contributor.authorChammas, Roger [UNIFESP]
dc.contributor.authorSaito, Renata de Freitas
dc.contributor.authorIqbal, Asif
dc.contributor.authorChudzinski-Tavassi, Ana Marisa [UNIFESP]
dc.coverageDordrecht
dc.date.accessioned2020-07-22T13:23:17Z
dc.date.available2020-07-22T13:23:17Z
dc.date.issued2016
dc.description.abstractDuring the last two decades, new insights into proteasome function and its role in several human diseases made it a potential therapeutic target. In this context, Amblyomin-X is a Kunitz-type FXa inhibitor similar to endogenous tissue factor pathway inhibitor (TFPI) and is a novel proteasome inhibitor. Herein, we have demonstrated Amblyomin-X cytotoxicity to different tumor cells lines such as pancreatic (Panc1, AsPC1BxPC3) and melanoma (SK-MEL-5 and SK-MEL-28). Of note, Amblyomin-X was not cytotoxic to normal human fibroblast cells. In addition, Amblyomin-X promoted accumulation of ER stress markers (GRP78 and GADD153) in sensitive (SK-MEL-28) and bortezomib-resistant (Mia-PaCa-2) tumor cells. The intracellular calcium concentration [Ca2+] (i) was slightly modulated in human tumor cells (SK-MEL-28 and Mia-PaCa-2) after 24 h of Amblyomin-X treatment. Furthermore, Amblyomin-X induced mitochondrial dysfunction, cytochrome-c release, PARP cleavage, and activation of caspase cascade in both human tumor (SK-MEL-28 and Mia-PaCa-2) cells. These investigations might help in further understanding of the antitumor properties of Amblyomin-X.en
dc.description.affiliationButantan Inst, Biochem & Biophys Lab, Ave Vital Brazil 1500, BR-05503900 Sao Paulo, SP, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Biochem, Sao Paulo, SP, Brazil
dc.description.affiliationUniv Sao Paulo, Inst Chem, Dept Biochem, Sao Paulo, Brazil
dc.description.affiliationUniv Sao Paulo, Sch Med, Expt Oncol Med Invest Lab, LIM 24, Sao Paulo, SP, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Biochem, Sao Paulo, SP, Brazil
dc.description.provenanceMade available in DSpace on 2020-07-22T13:23:17Z (GMT). No. of bitstreams: 0 Previous issue date: 2016. Added 1 bitstream(s) on 2020-07-22T13:32:19Z : No. of bitstreams: 1 WOS000373610000011.pdf: 1777061 bytes, checksum: 6b734150e4b5ce241ff02233d93160e6 (MD5)en
dc.description.sourceWeb of Science
dc.description.sponsorshipSao Paulo Research Foundation (FAPESP)
dc.description.sponsorshipNational Council of Technological and Scientific Development (CNPq, INCTTox)
dc.description.sponsorshipCoordination of Improvement of Higher Education Personnel (CAPES)
dc.description.sponsorshipUniao Quimica Farmaceutica Nacional
dc.description.sponsorshipIDFAPESP: 2010/52669-3
dc.description.sponsorshipIDFAPESP: 2010/07958-7
dc.description.sponsorshipIDFAPESP: 2011/05969-4
dc.description.sponsorshipIDFAPESP: CAT/CEPID 1998/14307-9
dc.description.sponsorshipIDFAPESP: CETICs 2013/07467-1
dc.format.extent119-131
dc.identifierhttp://dx.doi.org/10.1007/s11010-016-2683-4
dc.identifier.citationMolecular And Cellular Biochemistry. Dordrecht, v. 415, p. 119-131, 2016.
dc.identifier.doi10.1007/s11010-016-2683-4
dc.identifier.fileWOS000373610000011.pdf
dc.identifier.issn0300-8177
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/56153
dc.identifier.wosWOS:000373610000011
dc.language.isoeng
dc.publisherSpringer
dc.relation.ispartofMolecular And Cellular Biochemistry
dc.rightsAcesso aberto
dc.subjectAmblyomin-Xen
dc.subjectKunitz-type inhibitoren
dc.subjectProteasome inhibitoren
dc.subjectEndoplasmic reticulum stressen
dc.subjectAntitumor drug candidateen
dc.titleAmblyomin-X induces ER stress, mitochondrial dysfunction, and caspase activation in human melanoma and pancreatic tumor cellen
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