2-Dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione inhibits the growth and metastasis of breast carcinoma in mice

Abstract Metastasis causes approximately 90% of breast cancer-related deaths in women. Previously, we have demonstrated that 2-dodecyl-6-methoxycyclohexa-2,5-diene- 1,4-dione (DMDD) remarkably inhibited the growth of human breast cancer cells with little toxicity. In this study, we investigated the...

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Autores principales:	Chunxia Chen, Zhihuan Nong, Qiuqiao Xie, Junhui He, Wene Cai, Xiuneng Tang, Xiaoyu Chen, Renbin Huang, Ying Gao
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/77673c71faa84693863c06b8299b3a3c
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spelling	oai:doaj.org-article:77673c71faa84693863c06b8299b3a3c2021-12-02T15:06:19Z2-Dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione inhibits the growth and metastasis of breast carcinoma in mice10.1038/s41598-017-07162-32045-2322https://doaj.org/article/77673c71faa84693863c06b8299b3a3c2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07162-3https://doaj.org/toc/2045-2322Abstract Metastasis causes approximately 90% of breast cancer-related deaths in women. Previously, we have demonstrated that 2-dodecyl-6-methoxycyclohexa-2,5-diene- 1,4-dione (DMDD) remarkably inhibited the growth of human breast cancer cells with little toxicity. In this study, we investigated the toxicity and efficacy of DMDD to treat metastatic breast tumors using an in vivo mouse model of the 4T1 mammary carcinoma. DMDD caused no observable toxicity and significantly extended the survival of 4T1 tumor-bearing mice. DMDD effectively inhibited the growth of 4T1 cells in vitro, and suppressed the growth and metastasis of mammary tumor in vivo. The levels of inflammatory cytokines in the serum (TNF-α, IL-6, IL-12, TGF-β, and VEGF) were down regulated by DMDD. Immunohistochemical analysis demonstrated that the inhibition of tumor growth and metastasis was associated with activation of Bax, cleaved caspases-3 and -9, and down-regulation of Bcl-2, MMP-2 and -9, NF-κB and IκBα. We speculate that DMDD inhibits cytokine production in the tumor cells in mice, which leads to deactivation of NF-κB pathway, and consequently inhibits the expression of many anti-apoptosis and metastasis-promoting genes, such as Bcl-2 and MMPs. Collectively, our results demonstrate the potential of DMDD as a safe and effective antitumor agent in the treatment of late-stage breast cancer.Chunxia ChenZhihuan NongQiuqiao XieJunhui HeWene CaiXiuneng TangXiaoyu ChenRenbin HuangYing GaoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chunxia Chen Zhihuan Nong Qiuqiao Xie Junhui He Wene Cai Xiuneng Tang Xiaoyu Chen Renbin Huang Ying Gao 2-Dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione inhibits the growth and metastasis of breast carcinoma in mice
description	Abstract Metastasis causes approximately 90% of breast cancer-related deaths in women. Previously, we have demonstrated that 2-dodecyl-6-methoxycyclohexa-2,5-diene- 1,4-dione (DMDD) remarkably inhibited the growth of human breast cancer cells with little toxicity. In this study, we investigated the toxicity and efficacy of DMDD to treat metastatic breast tumors using an in vivo mouse model of the 4T1 mammary carcinoma. DMDD caused no observable toxicity and significantly extended the survival of 4T1 tumor-bearing mice. DMDD effectively inhibited the growth of 4T1 cells in vitro, and suppressed the growth and metastasis of mammary tumor in vivo. The levels of inflammatory cytokines in the serum (TNF-α, IL-6, IL-12, TGF-β, and VEGF) were down regulated by DMDD. Immunohistochemical analysis demonstrated that the inhibition of tumor growth and metastasis was associated with activation of Bax, cleaved caspases-3 and -9, and down-regulation of Bcl-2, MMP-2 and -9, NF-κB and IκBα. We speculate that DMDD inhibits cytokine production in the tumor cells in mice, which leads to deactivation of NF-κB pathway, and consequently inhibits the expression of many anti-apoptosis and metastasis-promoting genes, such as Bcl-2 and MMPs. Collectively, our results demonstrate the potential of DMDD as a safe and effective antitumor agent in the treatment of late-stage breast cancer.
format	article
author	Chunxia Chen Zhihuan Nong Qiuqiao Xie Junhui He Wene Cai Xiuneng Tang Xiaoyu Chen Renbin Huang Ying Gao
author_facet	Chunxia Chen Zhihuan Nong Qiuqiao Xie Junhui He Wene Cai Xiuneng Tang Xiaoyu Chen Renbin Huang Ying Gao
author_sort	Chunxia Chen
title	2-Dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione inhibits the growth and metastasis of breast carcinoma in mice
title_short	2-Dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione inhibits the growth and metastasis of breast carcinoma in mice
title_full	2-Dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione inhibits the growth and metastasis of breast carcinoma in mice
title_fullStr	2-Dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione inhibits the growth and metastasis of breast carcinoma in mice
title_full_unstemmed	2-Dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione inhibits the growth and metastasis of breast carcinoma in mice
title_sort	2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione inhibits the growth and metastasis of breast carcinoma in mice
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/77673c71faa84693863c06b8299b3a3c
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2-Dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione inhibits the growth and metastasis of breast carcinoma in mice

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