In situ delivery of biobutyrate by probiotic Escherichia coli for cancer therapy

Abstract Butyrate has a bioactive function to reduce carcinogenesis. To achieve targeted cancer therapy, this study developed bacterial cancer therapy (BCT) with butyrate as a payload. By metabolic engineering, Escherichia coli Nissle 1917 (EcN) was reprogrammed to synthesize butyrate (referred to a...

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Autores principales:	Chung-Jen Chiang, Yan-Hong Hong
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7ef2b68940fa48df835a93d948504adf
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spelling	oai:doaj.org-article:7ef2b68940fa48df835a93d948504adf2021-12-02T18:02:22ZIn situ delivery of biobutyrate by probiotic Escherichia coli for cancer therapy10.1038/s41598-021-97457-32045-2322https://doaj.org/article/7ef2b68940fa48df835a93d948504adf2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97457-3https://doaj.org/toc/2045-2322Abstract Butyrate has a bioactive function to reduce carcinogenesis. To achieve targeted cancer therapy, this study developed bacterial cancer therapy (BCT) with butyrate as a payload. By metabolic engineering, Escherichia coli Nissle 1917 (EcN) was reprogrammed to synthesize butyrate (referred to as biobutyrate) and designated EcN-BUT. The adopted strategy includes construction of a synthetic pathway for biobutyrate and the rational design of central metabolism to increase the production of biobutyrate at the expense of acetate. With glucose, EcN-BUT produced primarily biobutyrate under the hypoxic condition. Furthermore, human colorectal cancer cell was administrated with the produced biobutyrate. It caused the cell cycle arrest at the G1 phase and induced the mitochondrial apoptosis pathway independent of p53. In the tumor-bearing mice, the injected EcN-BUT exhibited tumor-specific colonization and significantly reduced the tumor volume by 70%. Overall, this study opens a new avenue for BCT based on biobutyrate.Chung-Jen ChiangYan-Hong HongNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chung-Jen Chiang Yan-Hong Hong In situ delivery of biobutyrate by probiotic Escherichia coli for cancer therapy
description	Abstract Butyrate has a bioactive function to reduce carcinogenesis. To achieve targeted cancer therapy, this study developed bacterial cancer therapy (BCT) with butyrate as a payload. By metabolic engineering, Escherichia coli Nissle 1917 (EcN) was reprogrammed to synthesize butyrate (referred to as biobutyrate) and designated EcN-BUT. The adopted strategy includes construction of a synthetic pathway for biobutyrate and the rational design of central metabolism to increase the production of biobutyrate at the expense of acetate. With glucose, EcN-BUT produced primarily biobutyrate under the hypoxic condition. Furthermore, human colorectal cancer cell was administrated with the produced biobutyrate. It caused the cell cycle arrest at the G1 phase and induced the mitochondrial apoptosis pathway independent of p53. In the tumor-bearing mice, the injected EcN-BUT exhibited tumor-specific colonization and significantly reduced the tumor volume by 70%. Overall, this study opens a new avenue for BCT based on biobutyrate.
format	article
author	Chung-Jen Chiang Yan-Hong Hong
author_facet	Chung-Jen Chiang Yan-Hong Hong
author_sort	Chung-Jen Chiang
title	In situ delivery of biobutyrate by probiotic Escherichia coli for cancer therapy
title_short	In situ delivery of biobutyrate by probiotic Escherichia coli for cancer therapy
title_full	In situ delivery of biobutyrate by probiotic Escherichia coli for cancer therapy
title_fullStr	In situ delivery of biobutyrate by probiotic Escherichia coli for cancer therapy
title_full_unstemmed	In situ delivery of biobutyrate by probiotic Escherichia coli for cancer therapy
title_sort	in situ delivery of biobutyrate by probiotic escherichia coli for cancer therapy
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/7ef2b68940fa48df835a93d948504adf
work_keys_str_mv	AT chungjenchiang insitudeliveryofbiobutyratebyprobioticescherichiacoliforcancertherapy AT yanhonghong insitudeliveryofbiobutyratebyprobioticescherichiacoliforcancertherapy
_version_	1718378937144311808

In situ delivery of biobutyrate by probiotic Escherichia coli for cancer therapy

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