Antitumor activity of irradiated riboflavin on human renal carcinoma cell line 786-O
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://link.springer.com/article/10.1007%2Fs13277-014-2675-5 http://hdl.handle.net/11449/128464 |
Resumo: | Riboflavin (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. |
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Antitumor activity of irradiated riboflavin on human renal carcinoma cell line 786-ORiboflavinIrradiated riboflavinAntitumor activityRenal cell carcinomaRiboflavin (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.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Estadual Paulista (UNESP) - Faculdade de Odontologia de Araçatuba, Departamento de Ciências Básicas, Araçatuba, SP 16018-805, BrazilUniversidade Estadual de Campinas (UNICAMP) - Instituto de Biologia, Departamento de Bioquímica, Campinas, SP 13083-970, BrazilUniversidade Estadual Paulista (UNESP) - Faculdade de Odontologia de Araçatuba, Departamento de Ciências Básicas, Araçatuba, SP 16018-805, BrazilFAPESP: 10/50356-8CNPq: 471151/2011-4SpringerUniversidade Estadual de Campinas (UNICAMP)Universidade Estadual Paulista (Unesp)Chaves Neto, Antonio Hernandes [UNESP]Pelizzaro-Rocha, Karin JulianeFernandes, Maruska NeufertFerreira-Halder, Carmen Verissima2015-10-21T13:10:06Z2015-10-21T13:10:06Z2015-02-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article595-604http://link.springer.com/article/10.1007%2Fs13277-014-2675-5Tumor Biology. Dordrecht: Springer, v. 36, n. 2, p. 595-604, 2015.1010-4283http://hdl.handle.net/11449/12846410.1007/s13277-014-2675-5WOS:000350478200017Web of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengTumor Biology1,149info:eu-repo/semantics/openAccess2021-10-23T22:04:28Zoai:repositorio.unesp.br:11449/128464Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462021-10-23T22:04:28Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Antitumor activity of irradiated riboflavin on human renal carcinoma cell line 786-O |
title |
Antitumor activity of irradiated riboflavin on human renal carcinoma cell line 786-O |
spellingShingle |
Antitumor activity of irradiated riboflavin on human renal carcinoma cell line 786-O Chaves Neto, Antonio Hernandes [UNESP] Riboflavin Irradiated riboflavin Antitumor activity Renal cell carcinoma |
title_short |
Antitumor activity of irradiated riboflavin on human renal carcinoma cell line 786-O |
title_full |
Antitumor activity of irradiated riboflavin on human renal carcinoma cell line 786-O |
title_fullStr |
Antitumor activity of irradiated riboflavin on human renal carcinoma cell line 786-O |
title_full_unstemmed |
Antitumor activity of irradiated riboflavin on human renal carcinoma cell line 786-O |
title_sort |
Antitumor activity of irradiated riboflavin on human renal carcinoma cell line 786-O |
author |
Chaves Neto, Antonio Hernandes [UNESP] |
author_facet |
Chaves Neto, Antonio Hernandes [UNESP] Pelizzaro-Rocha, Karin Juliane Fernandes, Maruska Neufert Ferreira-Halder, Carmen Verissima |
author_role |
author |
author2 |
Pelizzaro-Rocha, Karin Juliane Fernandes, Maruska Neufert Ferreira-Halder, Carmen Verissima |
author2_role |
author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual de Campinas (UNICAMP) Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Chaves Neto, Antonio Hernandes [UNESP] Pelizzaro-Rocha, Karin Juliane Fernandes, Maruska Neufert Ferreira-Halder, Carmen Verissima |
dc.subject.por.fl_str_mv |
Riboflavin Irradiated riboflavin Antitumor activity Renal cell carcinoma |
topic |
Riboflavin Irradiated riboflavin Antitumor activity Renal cell carcinoma |
description |
Riboflavin (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. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-10-21T13:10:06Z 2015-10-21T13:10:06Z 2015-02-01 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://link.springer.com/article/10.1007%2Fs13277-014-2675-5 Tumor Biology. Dordrecht: Springer, v. 36, n. 2, p. 595-604, 2015. 1010-4283 http://hdl.handle.net/11449/128464 10.1007/s13277-014-2675-5 WOS:000350478200017 |
url |
http://link.springer.com/article/10.1007%2Fs13277-014-2675-5 http://hdl.handle.net/11449/128464 |
identifier_str_mv |
Tumor Biology. Dordrecht: Springer, v. 36, n. 2, p. 595-604, 2015. 1010-4283 10.1007/s13277-014-2675-5 WOS:000350478200017 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Tumor Biology 1,149 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
595-604 |
dc.publisher.none.fl_str_mv |
Springer |
publisher.none.fl_str_mv |
Springer |
dc.source.none.fl_str_mv |
Web of Science reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
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1799965638926532608 |