Effect of melatonin on tumor growth and angiogenesis in xenograft model of breast cancer
Autor(a) principal: | |
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Data de Publicação: | 2014 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1371/journal.pone.0085311 http://hdl.handle.net/11449/111554 |
Resumo: | As neovascularization is essential for tumor growth and metastasis, controlling angiogenesis is a promising tactic in limiting cancer progression. Melatonin has been studied for their inhibitory properties on angiogenesis in cancer. We performed an in vivo study to evaluate the effects of melatonin treatment on angiogenesis in breast cancer. Cell viability was measured by MTT assay after melatonin treatment in triple-negative breast cancer cells (MDA-MB-231). After, cells were implanted in athymic nude mice and treated with melatonin or vehicle daily, administered intraperitoneally 1 hour before turning the room light off. Volume of the tumors was measured weekly with a digital caliper and at the end of treatments animals underwent single photon emission computed tomography (SPECT) with Technetium-99m tagged vascular endothelial growth factor (VEGF) C to detect in vivo angiogenesis. In addition, expression of pro-angiogenic/growth factors in the tumor extracts was evaluated by membrane antibody array and collected tumor tissues were analyzed with histochemical staining. Melatonin in vitro treatment (1 mM) decreased cell viability (p<0.05). The breast cancer xenografts nude mice treated with melatonin showed reduced tumor size and cell proliferation (Ki-67) compared to control animals after 21 days of treatment (p<0.05). Expression of VEGF receptor 2 decreased significantly in the treated animals compared to that of control when determined by immunohistochemistry (p<0.05) but the changes were not significant on SPECT (p>0.05) images. In addition, there was a decrease of micro-vessel density (Von Willebrand Factor) in melatonin treated mice (p<0.05). However, semiquantitative densitometry analysis of membrane array indicated increased expression of epidermal growth factor receptor and insulin-like growth factor 1 in treated tumors compared to vehicle treated tumors (p<0.05). In conclusion, melatonin treatment showed effectiveness in reducing tumor growth and cell proliferation, as well as in the inhibition of angiogenesis. |
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Effect of melatonin on tumor growth and angiogenesis in xenograft model of breast cancerAs neovascularization is essential for tumor growth and metastasis, controlling angiogenesis is a promising tactic in limiting cancer progression. Melatonin has been studied for their inhibitory properties on angiogenesis in cancer. We performed an in vivo study to evaluate the effects of melatonin treatment on angiogenesis in breast cancer. Cell viability was measured by MTT assay after melatonin treatment in triple-negative breast cancer cells (MDA-MB-231). After, cells were implanted in athymic nude mice and treated with melatonin or vehicle daily, administered intraperitoneally 1 hour before turning the room light off. Volume of the tumors was measured weekly with a digital caliper and at the end of treatments animals underwent single photon emission computed tomography (SPECT) with Technetium-99m tagged vascular endothelial growth factor (VEGF) C to detect in vivo angiogenesis. In addition, expression of pro-angiogenic/growth factors in the tumor extracts was evaluated by membrane antibody array and collected tumor tissues were analyzed with histochemical staining. Melatonin in vitro treatment (1 mM) decreased cell viability (p<0.05). The breast cancer xenografts nude mice treated with melatonin showed reduced tumor size and cell proliferation (Ki-67) compared to control animals after 21 days of treatment (p<0.05). Expression of VEGF receptor 2 decreased significantly in the treated animals compared to that of control when determined by immunohistochemistry (p<0.05) but the changes were not significant on SPECT (p>0.05) images. In addition, there was a decrease of micro-vessel density (Von Willebrand Factor) in melatonin treated mice (p<0.05). However, semiquantitative densitometry analysis of membrane array indicated increased expression of epidermal growth factor receptor and insulin-like growth factor 1 in treated tumors compared to vehicle treated tumors (p<0.05). In conclusion, melatonin treatment showed effectiveness in reducing tumor growth and cell proliferation, as well as in the inhibition of angiogenesis.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)NIHUniv Estadual Paulista, Dept Biol, Sao Paulo, BrazilFac Med Sao Jose Rio Preto, Dept Mol Biol, Lab Invest Mol Canc, Sao Paulo, BrazilHenry Ford Hosp, Dept Radiol, Cellular & Mol Imaging Lab, Detroit, MI 48202 USAFac Med Sao Jose Rio Preto, Dept Mol Biol, Sao Paulo, BrazilUniv Estadual Paulista, Dept Biol, Sao Paulo, BrazilFAPESP: 11/01052-9FAPESP: 11/01054-1FAPESP: 12/05065-0NIHR01CA160216NIHR01CA172048Public Library ScienceUniversidade Estadual Paulista (Unesp)Fac Med Sao Jose Rio PretoHenry Ford HospJardim-Perassi, Bruna Victorasso [UNESP]Arbab, Ali S.Ferreira, Livia Carvalho [UNESP]Borin, Thaiz FerrazVarma, Nadimpalli R. S.Iskander, A. S. M.Shankar, AdarshAli, Meser M.Pires de Campos Zuccari, Debora Aparecida2014-12-03T13:08:45Z2014-12-03T13:08:45Z2014-01-09info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article11application/pdfhttp://dx.doi.org/10.1371/journal.pone.0085311Plos One. San Francisco: Public Library Science, v. 9, n. 1, 11 p., 2014.1932-6203http://hdl.handle.net/11449/11155410.1371/journal.pone.0085311WOS:000329866300068WOS000329866300068.pdfWeb of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengPLOS ONE2.7661,164info:eu-repo/semantics/openAccess2024-01-01T06:20:42Zoai:repositorio.unesp.br:11449/111554Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-01-01T06:20:42Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Effect of melatonin on tumor growth and angiogenesis in xenograft model of breast cancer |
title |
Effect of melatonin on tumor growth and angiogenesis in xenograft model of breast cancer |
spellingShingle |
Effect of melatonin on tumor growth and angiogenesis in xenograft model of breast cancer Jardim-Perassi, Bruna Victorasso [UNESP] |
title_short |
Effect of melatonin on tumor growth and angiogenesis in xenograft model of breast cancer |
title_full |
Effect of melatonin on tumor growth and angiogenesis in xenograft model of breast cancer |
title_fullStr |
Effect of melatonin on tumor growth and angiogenesis in xenograft model of breast cancer |
title_full_unstemmed |
Effect of melatonin on tumor growth and angiogenesis in xenograft model of breast cancer |
title_sort |
Effect of melatonin on tumor growth and angiogenesis in xenograft model of breast cancer |
author |
Jardim-Perassi, Bruna Victorasso [UNESP] |
author_facet |
Jardim-Perassi, Bruna Victorasso [UNESP] Arbab, Ali S. Ferreira, Livia Carvalho [UNESP] Borin, Thaiz Ferraz Varma, Nadimpalli R. S. Iskander, A. S. M. Shankar, Adarsh Ali, Meser M. Pires de Campos Zuccari, Debora Aparecida |
author_role |
author |
author2 |
Arbab, Ali S. Ferreira, Livia Carvalho [UNESP] Borin, Thaiz Ferraz Varma, Nadimpalli R. S. Iskander, A. S. M. Shankar, Adarsh Ali, Meser M. Pires de Campos Zuccari, Debora Aparecida |
author2_role |
author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) Fac Med Sao Jose Rio Preto Henry Ford Hosp |
dc.contributor.author.fl_str_mv |
Jardim-Perassi, Bruna Victorasso [UNESP] Arbab, Ali S. Ferreira, Livia Carvalho [UNESP] Borin, Thaiz Ferraz Varma, Nadimpalli R. S. Iskander, A. S. M. Shankar, Adarsh Ali, Meser M. Pires de Campos Zuccari, Debora Aparecida |
description |
As neovascularization is essential for tumor growth and metastasis, controlling angiogenesis is a promising tactic in limiting cancer progression. Melatonin has been studied for their inhibitory properties on angiogenesis in cancer. We performed an in vivo study to evaluate the effects of melatonin treatment on angiogenesis in breast cancer. Cell viability was measured by MTT assay after melatonin treatment in triple-negative breast cancer cells (MDA-MB-231). After, cells were implanted in athymic nude mice and treated with melatonin or vehicle daily, administered intraperitoneally 1 hour before turning the room light off. Volume of the tumors was measured weekly with a digital caliper and at the end of treatments animals underwent single photon emission computed tomography (SPECT) with Technetium-99m tagged vascular endothelial growth factor (VEGF) C to detect in vivo angiogenesis. In addition, expression of pro-angiogenic/growth factors in the tumor extracts was evaluated by membrane antibody array and collected tumor tissues were analyzed with histochemical staining. Melatonin in vitro treatment (1 mM) decreased cell viability (p<0.05). The breast cancer xenografts nude mice treated with melatonin showed reduced tumor size and cell proliferation (Ki-67) compared to control animals after 21 days of treatment (p<0.05). Expression of VEGF receptor 2 decreased significantly in the treated animals compared to that of control when determined by immunohistochemistry (p<0.05) but the changes were not significant on SPECT (p>0.05) images. In addition, there was a decrease of micro-vessel density (Von Willebrand Factor) in melatonin treated mice (p<0.05). However, semiquantitative densitometry analysis of membrane array indicated increased expression of epidermal growth factor receptor and insulin-like growth factor 1 in treated tumors compared to vehicle treated tumors (p<0.05). In conclusion, melatonin treatment showed effectiveness in reducing tumor growth and cell proliferation, as well as in the inhibition of angiogenesis. |
publishDate |
2014 |
dc.date.none.fl_str_mv |
2014-12-03T13:08:45Z 2014-12-03T13:08:45Z 2014-01-09 |
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://dx.doi.org/10.1371/journal.pone.0085311 Plos One. San Francisco: Public Library Science, v. 9, n. 1, 11 p., 2014. 1932-6203 http://hdl.handle.net/11449/111554 10.1371/journal.pone.0085311 WOS:000329866300068 WOS000329866300068.pdf |
url |
http://dx.doi.org/10.1371/journal.pone.0085311 http://hdl.handle.net/11449/111554 |
identifier_str_mv |
Plos One. San Francisco: Public Library Science, v. 9, n. 1, 11 p., 2014. 1932-6203 10.1371/journal.pone.0085311 WOS:000329866300068 WOS000329866300068.pdf |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
PLOS ONE 2.766 1,164 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
11 application/pdf |
dc.publisher.none.fl_str_mv |
Public Library Science |
publisher.none.fl_str_mv |
Public Library Science |
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) |
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1803047216089137152 |