Identification of triptonide as a therapeutic agent for triple negative breast cancer treatment

Abstract Triple-negative breast cancer (TNBC) is associated with a high rate of early recurrence and distant metastasis, frequent development of therapeutic resistance, and a poor prognosis. There is a lack of targeted therapies for this aggressive subtype of breast cancer. Identifying novel effecti...

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Autores principales:	Bowen Gao, Jiongyu Chen, Bingchen Han, Xinfeng Zhang, Jijun Hao, Armando E. Giuliano, Yukun Cui, Xiaojiang Cui
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0c576c9d1a8f4aa88792c764c17985e6
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spelling	oai:doaj.org-article:0c576c9d1a8f4aa88792c764c17985e62021-12-02T10:48:31ZIdentification of triptonide as a therapeutic agent for triple negative breast cancer treatment10.1038/s41598-021-82128-02045-2322https://doaj.org/article/0c576c9d1a8f4aa88792c764c17985e62021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82128-0https://doaj.org/toc/2045-2322Abstract Triple-negative breast cancer (TNBC) is associated with a high rate of early recurrence and distant metastasis, frequent development of therapeutic resistance, and a poor prognosis. There is a lack of targeted therapies for this aggressive subtype of breast cancer. Identifying novel effective treatment modalities for TNBC remains an urgent and unmet clinical need. In this study, we investigated the anti-cancer effect of triptonide, a natural compound derived from the traditional Chinese medicinal herb Tripterygium wilfordii Hook F, in TNBC. We found that triptonide inhibits human TNBC cell growth in vitro and growth of TNBC xenograft mammary tumors. It induces apoptosis and suppresses stem-like properties as indicated by reduced mammosphere formation and aldehyde dehydrogenase activity in TNBC cells. We show that triptonide downregulates multiple cancer stem cell-associated genes but upregulates SNAI1 gene expression. In support of SNAI1 induction as a negative feedback response to triptonide treatment, in vitro-derived triptonide-resistant HCC1806 cells display a markedly higher expression of SNAI1 compared with parental cells. Mechanistically, the increase of SNAI1 expression is mediated by the activation of JNK signaling, but not by ERK and AKT, two well-established SNAI1 regulators. Furthermore, knockdown of SNAI1 in the triptonide-resistant HCC1806 cells increases sensitivity to triptonide and reduces mammosphere formation. These results indicate that triptonide holds promise as a novel anti-tumor agent for TNBC treatment. Our study also reveals a SNAI1-associated feedback mechanism which may lead to acquired resistance to triptonide.Bowen GaoJiongyu ChenBingchen HanXinfeng ZhangJijun HaoArmando E. GiulianoYukun CuiXiaojiang CuiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bowen Gao Jiongyu Chen Bingchen Han Xinfeng Zhang Jijun Hao Armando E. Giuliano Yukun Cui Xiaojiang Cui Identification of triptonide as a therapeutic agent for triple negative breast cancer treatment
description	Abstract Triple-negative breast cancer (TNBC) is associated with a high rate of early recurrence and distant metastasis, frequent development of therapeutic resistance, and a poor prognosis. There is a lack of targeted therapies for this aggressive subtype of breast cancer. Identifying novel effective treatment modalities for TNBC remains an urgent and unmet clinical need. In this study, we investigated the anti-cancer effect of triptonide, a natural compound derived from the traditional Chinese medicinal herb Tripterygium wilfordii Hook F, in TNBC. We found that triptonide inhibits human TNBC cell growth in vitro and growth of TNBC xenograft mammary tumors. It induces apoptosis and suppresses stem-like properties as indicated by reduced mammosphere formation and aldehyde dehydrogenase activity in TNBC cells. We show that triptonide downregulates multiple cancer stem cell-associated genes but upregulates SNAI1 gene expression. In support of SNAI1 induction as a negative feedback response to triptonide treatment, in vitro-derived triptonide-resistant HCC1806 cells display a markedly higher expression of SNAI1 compared with parental cells. Mechanistically, the increase of SNAI1 expression is mediated by the activation of JNK signaling, but not by ERK and AKT, two well-established SNAI1 regulators. Furthermore, knockdown of SNAI1 in the triptonide-resistant HCC1806 cells increases sensitivity to triptonide and reduces mammosphere formation. These results indicate that triptonide holds promise as a novel anti-tumor agent for TNBC treatment. Our study also reveals a SNAI1-associated feedback mechanism which may lead to acquired resistance to triptonide.
format	article
author	Bowen Gao Jiongyu Chen Bingchen Han Xinfeng Zhang Jijun Hao Armando E. Giuliano Yukun Cui Xiaojiang Cui
author_facet	Bowen Gao Jiongyu Chen Bingchen Han Xinfeng Zhang Jijun Hao Armando E. Giuliano Yukun Cui Xiaojiang Cui
author_sort	Bowen Gao
title	Identification of triptonide as a therapeutic agent for triple negative breast cancer treatment
title_short	Identification of triptonide as a therapeutic agent for triple negative breast cancer treatment
title_full	Identification of triptonide as a therapeutic agent for triple negative breast cancer treatment
title_fullStr	Identification of triptonide as a therapeutic agent for triple negative breast cancer treatment
title_full_unstemmed	Identification of triptonide as a therapeutic agent for triple negative breast cancer treatment
title_sort	identification of triptonide as a therapeutic agent for triple negative breast cancer treatment
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0c576c9d1a8f4aa88792c764c17985e6
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Identification of triptonide as a therapeutic agent for triple negative breast cancer treatment

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