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Melatonin Attenuates Her-2, p38 MAPK, p-AKT, and mTOR Levels in Ovarian Carcinoma of Ethanol-Preferring Rats
Epidermal growth factor receptors 2 (Her-2) and 4 (Her-4) are closely associated with ovarian cancer (OC) progression and metastasis, and a more complete understanding of these signaling pathways allow the development of new therapeutic strategies. Melatonin (Mel) is recognized as having several ant...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4216796/ https://www.ncbi.nlm.nih.gov/pubmed/25368672 http://dx.doi.org/10.7150/jca.10196 |
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author | Ferreira, Grazielle M. Martinez, Marcelo Camargo, Isabel Cristina C. Domeniconi, Raquel F. Martinez, Francisco Eduardo Chuffa, Luiz Gustavo A. |
author_facet | Ferreira, Grazielle M. Martinez, Marcelo Camargo, Isabel Cristina C. Domeniconi, Raquel F. Martinez, Francisco Eduardo Chuffa, Luiz Gustavo A. |
author_sort | Ferreira, Grazielle M. |
collection | PubMed |
description | Epidermal growth factor receptors 2 (Her-2) and 4 (Her-4) are closely associated with ovarian cancer (OC) progression and metastasis, and a more complete understanding of these signaling pathways allow the development of new therapeutic strategies. Melatonin (Mel) is recognized as having several anticancer properties and has been reported to modulate Her-2 system in aggressive tumors. Here, we investigated OC and the role of Mel therapy on the Her-2- and Her-4-signaling pathway related to downstream molecules in an ethanol-preferring rat model. To induce OC, the left ovary was injected directly with a single dose of 100 µg 7,12-dimethylbenz(a)anthracene (DMBA) dissolved in 10 µL of sesame oil under the bursa. Right ovaries were used as sham-surgery controls. After developing OC, half of the animals received i.p. injections of Mel (200 µg/100 g b.w./day) for 60 days. While Mel therapy was unable to reduce Her-4 and phosphoinositide 3-kinase (PI3K) levels, it was able to suppress the OC-related increase in the levels of the Her-2, p38 mitogen-activated protein kinases (p38 MAPK), protein kinase B (phospho-AKT), and mammalian target of rapamycin (mTOR). In addition, Mel significantly attenuated the expression of Her-2, p38 MAPK, and p-AKT, which are involved in OC signaling during ethanol intake. Collectively, our results suggest that Mel attenuates the Her-2-signaling pathway in OC of ethanol-preferring rats, providing an effective contribution for further development of adjuvant therapies. |
format | Online Article Text |
id | pubmed-4216796 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-42167962014-11-03 Melatonin Attenuates Her-2, p38 MAPK, p-AKT, and mTOR Levels in Ovarian Carcinoma of Ethanol-Preferring Rats Ferreira, Grazielle M. Martinez, Marcelo Camargo, Isabel Cristina C. Domeniconi, Raquel F. Martinez, Francisco Eduardo Chuffa, Luiz Gustavo A. J Cancer Research Paper Epidermal growth factor receptors 2 (Her-2) and 4 (Her-4) are closely associated with ovarian cancer (OC) progression and metastasis, and a more complete understanding of these signaling pathways allow the development of new therapeutic strategies. Melatonin (Mel) is recognized as having several anticancer properties and has been reported to modulate Her-2 system in aggressive tumors. Here, we investigated OC and the role of Mel therapy on the Her-2- and Her-4-signaling pathway related to downstream molecules in an ethanol-preferring rat model. To induce OC, the left ovary was injected directly with a single dose of 100 µg 7,12-dimethylbenz(a)anthracene (DMBA) dissolved in 10 µL of sesame oil under the bursa. Right ovaries were used as sham-surgery controls. After developing OC, half of the animals received i.p. injections of Mel (200 µg/100 g b.w./day) for 60 days. While Mel therapy was unable to reduce Her-4 and phosphoinositide 3-kinase (PI3K) levels, it was able to suppress the OC-related increase in the levels of the Her-2, p38 mitogen-activated protein kinases (p38 MAPK), protein kinase B (phospho-AKT), and mammalian target of rapamycin (mTOR). In addition, Mel significantly attenuated the expression of Her-2, p38 MAPK, and p-AKT, which are involved in OC signaling during ethanol intake. Collectively, our results suggest that Mel attenuates the Her-2-signaling pathway in OC of ethanol-preferring rats, providing an effective contribution for further development of adjuvant therapies. Ivyspring International Publisher 2014-10-03 /pmc/articles/PMC4216796/ /pubmed/25368672 http://dx.doi.org/10.7150/jca.10196 Text en © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. |
spellingShingle | Research Paper Ferreira, Grazielle M. Martinez, Marcelo Camargo, Isabel Cristina C. Domeniconi, Raquel F. Martinez, Francisco Eduardo Chuffa, Luiz Gustavo A. Melatonin Attenuates Her-2, p38 MAPK, p-AKT, and mTOR Levels in Ovarian Carcinoma of Ethanol-Preferring Rats |
title | Melatonin Attenuates Her-2, p38 MAPK, p-AKT, and mTOR Levels in Ovarian Carcinoma of Ethanol-Preferring Rats |
title_full | Melatonin Attenuates Her-2, p38 MAPK, p-AKT, and mTOR Levels in Ovarian Carcinoma of Ethanol-Preferring Rats |
title_fullStr | Melatonin Attenuates Her-2, p38 MAPK, p-AKT, and mTOR Levels in Ovarian Carcinoma of Ethanol-Preferring Rats |
title_full_unstemmed | Melatonin Attenuates Her-2, p38 MAPK, p-AKT, and mTOR Levels in Ovarian Carcinoma of Ethanol-Preferring Rats |
title_short | Melatonin Attenuates Her-2, p38 MAPK, p-AKT, and mTOR Levels in Ovarian Carcinoma of Ethanol-Preferring Rats |
title_sort | melatonin attenuates her-2, p38 mapk, p-akt, and mtor levels in ovarian carcinoma of ethanol-preferring rats |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4216796/ https://www.ncbi.nlm.nih.gov/pubmed/25368672 http://dx.doi.org/10.7150/jca.10196 |
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