Deguelin action involves c-Met and EGFR signaling pathways in triple negative breast cancer cells.

<h4>Background</h4>Treatment of breast cancer patients with antiestrogens and aromatase inhibitor(s) or Herceptin have shown significant success in steroid receptor positive or Her-2+ breast cancers respectively. However, choice of treatments for breast cancer patients with negative stat...

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Autores principales:	Rajeshwari Mehta, Harshadadevi Katta, Fatouma Alimirah, Rutulkumar Patel, Genoveva Murillo, Xinjian Peng, Miguel Muzzio, Rajendra G Mehta
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/39d2c5de925e46dda68a3b55ca44f64b
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spelling	oai:doaj.org-article:39d2c5de925e46dda68a3b55ca44f64b2021-11-18T07:42:30ZDeguelin action involves c-Met and EGFR signaling pathways in triple negative breast cancer cells.1932-620310.1371/journal.pone.0065113https://doaj.org/article/39d2c5de925e46dda68a3b55ca44f64b2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23762292/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Treatment of breast cancer patients with antiestrogens and aromatase inhibitor(s) or Herceptin have shown significant success in steroid receptor positive or Her-2+ breast cancers respectively. However, choice of treatments for breast cancer patients with negative status for estrogen, progesterone receptors and HER2/neu is limited. As a result, search for appropriate therapy regimen for these triple negative breast cancers (TNBC) has become a major focus of investigations for many laboratories. Recently, Deguelin, a natural product isolated from African plant Mundulea sericea (Leguminossae) has shown both antiproliferative actions in various cancers including breast as well as chemoprenventive activity against carcinogen induced experimental cancers. In this report we evaluated efficacy and mechanism of action of Deguelin in triple negative breast cancer cell lines.<h4>Methods/findings</h4>In vitro, Deguelin in a dose and time dependent manner inhibited the growth of MDA-MB-231, MDA-MB-468, BT-549 and BT-20 cells. Deguelin (2 or 4 mg/kg body weight), when injected intraperitoneally, reduced the in vivo tumor growth of MDA-MB-231 cells transplanted subcutaneously in athymic mice. Moreover it was nontoxic as evident from daily observations on mobility, food and water consumption and comparison of bodyweight and other visceral organ weights with those in control animals at the termination of the study. The western blot analyses and immunostaining studies indicated that the deguelin effects may be mediated through EGFR-PAKT/c-Met p-ERK and NF-κB by down regulating their downstream targets such as p-STAT3, c-Myc, Survivin.<h4>Conclusion/significance</h4>These results suggest that Deguelin may have a significant therapeutic value for the treatment of TNBC patients.Rajeshwari MehtaHarshadadevi KattaFatouma AlimirahRutulkumar PatelGenoveva MurilloXinjian PengMiguel MuzzioRajendra G MehtaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 6, p e65113 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rajeshwari Mehta Harshadadevi Katta Fatouma Alimirah Rutulkumar Patel Genoveva Murillo Xinjian Peng Miguel Muzzio Rajendra G Mehta Deguelin action involves c-Met and EGFR signaling pathways in triple negative breast cancer cells.
description	<h4>Background</h4>Treatment of breast cancer patients with antiestrogens and aromatase inhibitor(s) or Herceptin have shown significant success in steroid receptor positive or Her-2+ breast cancers respectively. However, choice of treatments for breast cancer patients with negative status for estrogen, progesterone receptors and HER2/neu is limited. As a result, search for appropriate therapy regimen for these triple negative breast cancers (TNBC) has become a major focus of investigations for many laboratories. Recently, Deguelin, a natural product isolated from African plant Mundulea sericea (Leguminossae) has shown both antiproliferative actions in various cancers including breast as well as chemoprenventive activity against carcinogen induced experimental cancers. In this report we evaluated efficacy and mechanism of action of Deguelin in triple negative breast cancer cell lines.<h4>Methods/findings</h4>In vitro, Deguelin in a dose and time dependent manner inhibited the growth of MDA-MB-231, MDA-MB-468, BT-549 and BT-20 cells. Deguelin (2 or 4 mg/kg body weight), when injected intraperitoneally, reduced the in vivo tumor growth of MDA-MB-231 cells transplanted subcutaneously in athymic mice. Moreover it was nontoxic as evident from daily observations on mobility, food and water consumption and comparison of bodyweight and other visceral organ weights with those in control animals at the termination of the study. The western blot analyses and immunostaining studies indicated that the deguelin effects may be mediated through EGFR-PAKT/c-Met p-ERK and NF-κB by down regulating their downstream targets such as p-STAT3, c-Myc, Survivin.<h4>Conclusion/significance</h4>These results suggest that Deguelin may have a significant therapeutic value for the treatment of TNBC patients.
format	article
author	Rajeshwari Mehta Harshadadevi Katta Fatouma Alimirah Rutulkumar Patel Genoveva Murillo Xinjian Peng Miguel Muzzio Rajendra G Mehta
author_facet	Rajeshwari Mehta Harshadadevi Katta Fatouma Alimirah Rutulkumar Patel Genoveva Murillo Xinjian Peng Miguel Muzzio Rajendra G Mehta
author_sort	Rajeshwari Mehta
title	Deguelin action involves c-Met and EGFR signaling pathways in triple negative breast cancer cells.
title_short	Deguelin action involves c-Met and EGFR signaling pathways in triple negative breast cancer cells.
title_full	Deguelin action involves c-Met and EGFR signaling pathways in triple negative breast cancer cells.
title_fullStr	Deguelin action involves c-Met and EGFR signaling pathways in triple negative breast cancer cells.
title_full_unstemmed	Deguelin action involves c-Met and EGFR signaling pathways in triple negative breast cancer cells.
title_sort	deguelin action involves c-met and egfr signaling pathways in triple negative breast cancer cells.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/39d2c5de925e46dda68a3b55ca44f64b
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Deguelin action involves c-Met and EGFR signaling pathways in triple negative breast cancer cells.

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