Antitumor activity of irradiated riboflavin on human renal carcinoma cell line 786-O

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dc.contributor.authorChaves Neto, Antonio Hernandes [UNESP]
dc.contributor.authorPelizzaro-Rocha, Karin Juliane
dc.contributor.authorFernandes, Maruska Neufert
dc.contributor.authorFerreira-Halder, Carmen Verissima
dc.contributor.institutionUniversidade Estadual de Campinas (UNICAMP)
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.date.accessioned2015-10-21T13:10:06Z
dc.date.available2015-10-21T13:10:06Z
dc.date.issued2015-02-01
dc.description.abstractRiboflavin (vitamin B-2) is a precursor for coenzymes involved in energy production, biosynthesis, detoxification, and electron scavenging. Previously, we demonstrated that irradiated riboflavin (IR) has potential antitumoral effects against human leukemia cells (HL60), human prostate cancer cells (PC3), and mouse melanoma cells (B16F10) through a common mechanism that leads to apoptosis. Hence, we here investigated the effect of IR on 786-O cells, a known model cell line for clear cell renal cell carcinoma (CCRCC), which is characterized by high-risk metastasis and chemotherapy resistance. IR also induced cell death in 786-O cells by apoptosis, which was not prevented by antioxidant agents. IR treatment was characterized by downregulation of Fas ligand (TNF superfamily, member 6)/Fas (TNF receptor superfamily member 6) (FasL/Fas) and tumor necrosis factor receptor superfamily, member 1a (TNFR1)/TNFRSF1A-associated via death domain (TRADD)/TNF receptor-associated factor 2 (TRAF) signaling pathways (the extrinsic apoptosis pathway), while the intrinsic apoptotic pathway was upregulated, as observed by an elevated Bcl-2 associated x protein/B-cell CLL/lymphoma 2 (Bax/Bcl-2) ratio, reduced cellular inhibitor of apoptosis 1 (c-IAP1) expression, and increased expression of apoptosis-inducing factor (AIF). The observed cell death was caspase-dependent as proven by caspase 3 activation and poly(ADP-ribose) polymerase-1 (PARP) cleavage. IR-induced cell death was also associated with downregulation of v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homologue (avian)/protein serine/threonine kinase B/extracellular signal-regulated protein kinase 1/2 (Src/AKT/ERK1/2) pathway and activation of p38 MAP kinase (p38) and Jun-amino-terminal kinase (JNK). Interestingly, IR treatment leads to inhibition of matrix metalloproteinase-2 (MMP-2) activity and reduced expression of renal cancer aggressiveness markers caveolin-1, low molecular weight phosphotyrosine protein phosphatase (LMWPTP), and kinase insert domain receptor (a type III receptor tyrosine kinase) (VEGFR-2). Together, these results show the potential of IR for treating cancer.en
dc.description.affiliationUniversidade Estadual Paulista (UNESP) - Faculdade de Odontologia de Araçatuba, Departamento de Ciências Básicas, Araçatuba, SP 16018-805, Brazil
dc.description.affiliationUniversidade Estadual de Campinas (UNICAMP) - Instituto de Biologia, Departamento de Bioquímica, Campinas, SP 13083-970, Brazil
dc.description.affiliationUnespUniversidade Estadual Paulista (UNESP) - Faculdade de Odontologia de Araçatuba, Departamento de Ciências Básicas, Araçatuba, SP 16018-805, Brazil
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipIdFAPESP: 10/50356-8
dc.description.sponsorshipIdCNPq: 471151/2011-4
dc.format.extent595-604
dc.identifierhttp://link.springer.com/article/10.1007%2Fs13277-014-2675-5
dc.identifier.citationTumor Biology. Dordrecht: Springer, v. 36, n. 2, p. 595-604, 2015.
dc.identifier.doi10.1007/s13277-014-2675-5
dc.identifier.issn1010-4283
dc.identifier.urihttp://hdl.handle.net/11449/128464
dc.identifier.wosWOS:000350478200017
dc.language.isoeng
dc.publisherSpringer
dc.relation.ispartofTumor Biology
dc.relation.ispartofsjr1,149
dc.rights.accessRightsAcesso aberto
dc.sourceWeb of Science
dc.subjectRiboflavinen
dc.subjectIrradiated riboflavinen
dc.subjectAntitumor activityen
dc.subjectRenal cell carcinomaen
dc.titleAntitumor activity of irradiated riboflavin on human renal carcinoma cell line 786-Oen
dc.typeArtigo
dcterms.licensehttp://www.springer.com/open+access/authors+rights?SGWID=0-176704-12-683201-0
dcterms.rightsHolderSpringer
unesp.author.lattes1743697225702984[1]
unesp.author.orcid0000-0001-6481-5506[1]
unesp.campusUniversidade Estadual Paulista (Unesp), Faculdade de Odontologia, Araçatubapt

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