Luteolin inhibits lung metastasis, cell migration, and viability of triple-negative breast cancer cells

Matthew T Cook,1,2 Yayun Liang,1,2 Cynthia Besch-Williford,3 Salman M Hyder1,2 1Department of Biomedical Sciences, 2Dalton Cardiovascular Research Center, University of Missouri, 3IDEXX BioResearch, Columbia, MO, USA Abstract: Most breast cancer-related deaths from triple-negative breast cancer (TNB...

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Autores principales:	Cook MT, Liang Y, Besch-Williford C, Hyder SM
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	luteolin triple-negative breast cancer metastasis cell migration apoptosis VEGF Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/fd3d22c61bf7404f941c2b88be5ac680
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spelling	oai:doaj.org-article:fd3d22c61bf7404f941c2b88be5ac6802021-12-02T01:12:12ZLuteolin inhibits lung metastasis, cell migration, and viability of triple-negative breast cancer cells1179-1314https://doaj.org/article/fd3d22c61bf7404f941c2b88be5ac6802016-12-01T00:00:00Zhttps://www.dovepress.com/luteolin-inhibits-lung-metastasis-cell-migration-and-viability-of-trip-peer-reviewed-article-BCTThttps://doaj.org/toc/1179-1314Matthew T Cook,1,2 Yayun Liang,1,2 Cynthia Besch-Williford,3 Salman M Hyder1,2 1Department of Biomedical Sciences, 2Dalton Cardiovascular Research Center, University of Missouri, 3IDEXX BioResearch, Columbia, MO, USA Abstract: Most breast cancer-related deaths from triple-negative breast cancer (TNBC) occur following metastasis of cancer cells and development of tumors at secondary sites. Because TNBCs lack the three receptors targeted by current chemotherapeutic regimens, they are typically treated with extremely aggressive and highly toxic non-targeted treatment strategies. Women with TNBC frequently develop metastatic lesions originating from drug-resistant residual cells and have poor prognosis. For this reason, novel therapeutic strategies that are safer and more effective are sought. Luteolin (LU) is a naturally occurring, non-toxic plant compound that has proven effective against several types of cancer. With this in mind, we conducted in vivo and in vitro studies to determine whether LU might suppress metastasis of TNBC. In an in vivo mouse metastasis model, LU suppressed metastasis of human MDA-MB-435 and MDA-MB-231 (4175) LM2 TNBC cells to the lungs. In in vitro assays, LU inhibited cell migration and viability of MDA-MB-435 and MDA-MB-231 (4175) LM2 cells. Further, LU induced apoptosis in MDA-MB-231 (4175) LM2 cells. Relatively low levels (10 µM) of LU significantly inhibited vascular endothelial growth factor (VEGF) secretion in MDA-MB-231 (4175) LM2 cells, suggesting that it has the ability to suppress a potent angiogenic and cell survival factor. In addition, migration of MDA-MB-231 (4175) LM2 cells was inhibited upon exposure to an antibody against the VEGF receptor, KDR, but not by exposure to a VEGF165 antibody. Collectively, these data suggest that the anti-metastatic properties of LU may, in part, be due to its ability to block VEGF production and KDR-mediated activity, thereby inhibiting tumor cell migration. These studies suggest that LU deserves further investigation as a potential treatment option for women with TNBC. Keywords: luteolin, triple-negative breast cancer, metastasis, cell migration, apoptosis, VEGFCook MTLiang YBesch-Williford CHyder SMDove Medical Pressarticleluteolintriple-negative breast cancermetastasiscell migrationapoptosisVEGFNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENBreast Cancer: Targets and Therapy, Vol Volume 9, Pp 9-19 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	luteolin triple-negative breast cancer metastasis cell migration apoptosis VEGF Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	luteolin triple-negative breast cancer metastasis cell migration apoptosis VEGF Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cook MT Liang Y Besch-Williford C Hyder SM Luteolin inhibits lung metastasis, cell migration, and viability of triple-negative breast cancer cells
description	Matthew T Cook,1,2 Yayun Liang,1,2 Cynthia Besch-Williford,3 Salman M Hyder1,2 1Department of Biomedical Sciences, 2Dalton Cardiovascular Research Center, University of Missouri, 3IDEXX BioResearch, Columbia, MO, USA Abstract: Most breast cancer-related deaths from triple-negative breast cancer (TNBC) occur following metastasis of cancer cells and development of tumors at secondary sites. Because TNBCs lack the three receptors targeted by current chemotherapeutic regimens, they are typically treated with extremely aggressive and highly toxic non-targeted treatment strategies. Women with TNBC frequently develop metastatic lesions originating from drug-resistant residual cells and have poor prognosis. For this reason, novel therapeutic strategies that are safer and more effective are sought. Luteolin (LU) is a naturally occurring, non-toxic plant compound that has proven effective against several types of cancer. With this in mind, we conducted in vivo and in vitro studies to determine whether LU might suppress metastasis of TNBC. In an in vivo mouse metastasis model, LU suppressed metastasis of human MDA-MB-435 and MDA-MB-231 (4175) LM2 TNBC cells to the lungs. In in vitro assays, LU inhibited cell migration and viability of MDA-MB-435 and MDA-MB-231 (4175) LM2 cells. Further, LU induced apoptosis in MDA-MB-231 (4175) LM2 cells. Relatively low levels (10 µM) of LU significantly inhibited vascular endothelial growth factor (VEGF) secretion in MDA-MB-231 (4175) LM2 cells, suggesting that it has the ability to suppress a potent angiogenic and cell survival factor. In addition, migration of MDA-MB-231 (4175) LM2 cells was inhibited upon exposure to an antibody against the VEGF receptor, KDR, but not by exposure to a VEGF165 antibody. Collectively, these data suggest that the anti-metastatic properties of LU may, in part, be due to its ability to block VEGF production and KDR-mediated activity, thereby inhibiting tumor cell migration. These studies suggest that LU deserves further investigation as a potential treatment option for women with TNBC. Keywords: luteolin, triple-negative breast cancer, metastasis, cell migration, apoptosis, VEGF
format	article
author	Cook MT Liang Y Besch-Williford C Hyder SM
author_facet	Cook MT Liang Y Besch-Williford C Hyder SM
author_sort	Cook MT
title	Luteolin inhibits lung metastasis, cell migration, and viability of triple-negative breast cancer cells
title_short	Luteolin inhibits lung metastasis, cell migration, and viability of triple-negative breast cancer cells
title_full	Luteolin inhibits lung metastasis, cell migration, and viability of triple-negative breast cancer cells
title_fullStr	Luteolin inhibits lung metastasis, cell migration, and viability of triple-negative breast cancer cells
title_full_unstemmed	Luteolin inhibits lung metastasis, cell migration, and viability of triple-negative breast cancer cells
title_sort	luteolin inhibits lung metastasis, cell migration, and viability of triple-negative breast cancer cells
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/fd3d22c61bf7404f941c2b88be5ac680
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Luteolin inhibits lung metastasis, cell migration, and viability of triple-negative breast cancer cells

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