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A novel hydrazide compound exerts anti-metastatic effect against breast cancer

BACKGROUND: There are currently a number of barriers hindering the successful treatment of breast cancer, including the metastatic spread of cancer cells. In looking for new anticancer agents, we reported two novel hydrazide derivatives with anti-cancer activity in human breast cancer cells. The cur...

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Autores principales: Dehghani, Soudeh, Kooshafar, Zahra, Almasirad, Ali, Tahmasvand, Raheleh, Moayer, Fariborz, Muhammadnejad, Ahad, Shafiee, Samira, Salimi, Mona
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683344/
https://www.ncbi.nlm.nih.gov/pubmed/31387647
http://dx.doi.org/10.1186/s40659-019-0247-2
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author Dehghani, Soudeh
Kooshafar, Zahra
Almasirad, Ali
Tahmasvand, Raheleh
Moayer, Fariborz
Muhammadnejad, Ahad
Shafiee, Samira
Salimi, Mona
author_facet Dehghani, Soudeh
Kooshafar, Zahra
Almasirad, Ali
Tahmasvand, Raheleh
Moayer, Fariborz
Muhammadnejad, Ahad
Shafiee, Samira
Salimi, Mona
author_sort Dehghani, Soudeh
collection PubMed
description BACKGROUND: There are currently a number of barriers hindering the successful treatment of breast cancer, including the metastatic spread of cancer cells. In looking for new anticancer agents, we reported two novel hydrazide derivatives with anti-cancer activity in human breast cancer cells. The current study aims to explore the therapeutic potential of the most effective one, N'-((5-nitrothiophen-2-yl)methylene)-2-(phenylthio)benzohydrazide (compound B), on metastatic breast cancer, which is resistant to available chemotherapeutics. METHODS: 4T1 mammary carcinoma cells were inoculated into the fat pad mammary of 5–7-week-old female BALB/c mice and then the effective compound was intraperitoneally administered for 4 weeks. Proliferation index and angiogenesis in tumor and lung tissues were examined with immunohistochemistry. In vitro assessments were also carried out to evaluate the effect of the compound on invasion of MDA-MB-231 cells. RESULTS: Our results demonstrated that this effective derivative significantly inhibited invasion of MDA-MB-231 cells in vitro as shown by Matrigel assay and quantitative real-time method for MMP-9 expression after 48 h of treatment. Daily administration of the compound suppressed the growth of primary tumor and its metastasis to lung, which was confirmed by H&E experiment at a dose of 1 mg/kg in a well-known metastatic model of 4T1 breast cancer in syngeneic BALB/c mice. These outcomes were supported by the immunohistochemical examinations of the tumor and lung tissues of mice. Tumors and lungs in mice treated with the effective compound showed a reduced proliferation index and a smaller microvessel density compared to the control. CONCLUSION: This study highlights an anti-metastatic role for a novel hydrazide derivative in both in vitro and in vivo models of breast cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40659-019-0247-2) contains supplementary material, which is available to authorized users.
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spelling pubmed-66833442019-08-09 A novel hydrazide compound exerts anti-metastatic effect against breast cancer Dehghani, Soudeh Kooshafar, Zahra Almasirad, Ali Tahmasvand, Raheleh Moayer, Fariborz Muhammadnejad, Ahad Shafiee, Samira Salimi, Mona Biol Res Research Article BACKGROUND: There are currently a number of barriers hindering the successful treatment of breast cancer, including the metastatic spread of cancer cells. In looking for new anticancer agents, we reported two novel hydrazide derivatives with anti-cancer activity in human breast cancer cells. The current study aims to explore the therapeutic potential of the most effective one, N'-((5-nitrothiophen-2-yl)methylene)-2-(phenylthio)benzohydrazide (compound B), on metastatic breast cancer, which is resistant to available chemotherapeutics. METHODS: 4T1 mammary carcinoma cells were inoculated into the fat pad mammary of 5–7-week-old female BALB/c mice and then the effective compound was intraperitoneally administered for 4 weeks. Proliferation index and angiogenesis in tumor and lung tissues were examined with immunohistochemistry. In vitro assessments were also carried out to evaluate the effect of the compound on invasion of MDA-MB-231 cells. RESULTS: Our results demonstrated that this effective derivative significantly inhibited invasion of MDA-MB-231 cells in vitro as shown by Matrigel assay and quantitative real-time method for MMP-9 expression after 48 h of treatment. Daily administration of the compound suppressed the growth of primary tumor and its metastasis to lung, which was confirmed by H&E experiment at a dose of 1 mg/kg in a well-known metastatic model of 4T1 breast cancer in syngeneic BALB/c mice. These outcomes were supported by the immunohistochemical examinations of the tumor and lung tissues of mice. Tumors and lungs in mice treated with the effective compound showed a reduced proliferation index and a smaller microvessel density compared to the control. CONCLUSION: This study highlights an anti-metastatic role for a novel hydrazide derivative in both in vitro and in vivo models of breast cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40659-019-0247-2) contains supplementary material, which is available to authorized users. BioMed Central 2019-08-06 /pmc/articles/PMC6683344/ /pubmed/31387647 http://dx.doi.org/10.1186/s40659-019-0247-2 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Dehghani, Soudeh
Kooshafar, Zahra
Almasirad, Ali
Tahmasvand, Raheleh
Moayer, Fariborz
Muhammadnejad, Ahad
Shafiee, Samira
Salimi, Mona
A novel hydrazide compound exerts anti-metastatic effect against breast cancer
title A novel hydrazide compound exerts anti-metastatic effect against breast cancer
title_full A novel hydrazide compound exerts anti-metastatic effect against breast cancer
title_fullStr A novel hydrazide compound exerts anti-metastatic effect against breast cancer
title_full_unstemmed A novel hydrazide compound exerts anti-metastatic effect against breast cancer
title_short A novel hydrazide compound exerts anti-metastatic effect against breast cancer
title_sort novel hydrazide compound exerts anti-metastatic effect against breast cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683344/
https://www.ncbi.nlm.nih.gov/pubmed/31387647
http://dx.doi.org/10.1186/s40659-019-0247-2
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