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Valeric Acid Suppresses Liver Cancer Development by Acting as a Novel HDAC Inhibitor

Liver cancer is the fastest growing cause of cancer deaths in the United States due to its aggressiveness and lack of effective therapies. The current preclinical study examines valeric acid (pentanoic acid [C(5)H(10)O(2)]), one of the main compounds of valerian root extract, for its therapeutic use...

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Detalles Bibliográficos
Autores principales: Han, Rui, Nusbaum, Olivia, Chen, Xinyi, Zhu, Yong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520432/
https://www.ncbi.nlm.nih.gov/pubmed/33024815
http://dx.doi.org/10.1016/j.omto.2020.08.017
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author Han, Rui
Nusbaum, Olivia
Chen, Xinyi
Zhu, Yong
author_facet Han, Rui
Nusbaum, Olivia
Chen, Xinyi
Zhu, Yong
author_sort Han, Rui
collection PubMed
description Liver cancer is the fastest growing cause of cancer deaths in the United States due to its aggressiveness and lack of effective therapies. The current preclinical study examines valeric acid (pentanoic acid [C(5)H(10)O(2)]), one of the main compounds of valerian root extract, for its therapeutic use in liver cancer treatment. Anticancer efficacy of valeric acid was tested in a series of in vitro assays and orthotopic xenograft mouse models. The molecular target of valeric acid was also predicted, followed by functional confirmation. Valeric acid has a broad spectrum of anticancer activity with specifically high cytotoxicity for liver cancer in cell proliferation, colony formation, wound healing, cell invasion, and 3D spheroid formation assays. Mouse models further demonstrate that systematic administration of lipid-based nanoparticle-encapsulated valeric acid significantly reduces the tumor burden and improves survival rate. Histone deacetylase (HDAC)-inhibiting functions of valeric acid are also revealed by a structural target prediction tool and HDAC activity assay. Further transcriptional profiling and network analyses illustrate that valeric acid affects several cancer-related pathways that may induce apoptosis. In summary, we demonstrate for the first time that valeric acid suppresses liver cancer development by acting as a potential novel HDAC inhibitor, which warrants further investigation on its therapeutic implications.
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spelling pubmed-75204322020-10-05 Valeric Acid Suppresses Liver Cancer Development by Acting as a Novel HDAC Inhibitor Han, Rui Nusbaum, Olivia Chen, Xinyi Zhu, Yong Mol Ther Oncolytics Original Article Liver cancer is the fastest growing cause of cancer deaths in the United States due to its aggressiveness and lack of effective therapies. The current preclinical study examines valeric acid (pentanoic acid [C(5)H(10)O(2)]), one of the main compounds of valerian root extract, for its therapeutic use in liver cancer treatment. Anticancer efficacy of valeric acid was tested in a series of in vitro assays and orthotopic xenograft mouse models. The molecular target of valeric acid was also predicted, followed by functional confirmation. Valeric acid has a broad spectrum of anticancer activity with specifically high cytotoxicity for liver cancer in cell proliferation, colony formation, wound healing, cell invasion, and 3D spheroid formation assays. Mouse models further demonstrate that systematic administration of lipid-based nanoparticle-encapsulated valeric acid significantly reduces the tumor burden and improves survival rate. Histone deacetylase (HDAC)-inhibiting functions of valeric acid are also revealed by a structural target prediction tool and HDAC activity assay. Further transcriptional profiling and network analyses illustrate that valeric acid affects several cancer-related pathways that may induce apoptosis. In summary, we demonstrate for the first time that valeric acid suppresses liver cancer development by acting as a potential novel HDAC inhibitor, which warrants further investigation on its therapeutic implications. American Society of Gene & Cell Therapy 2020-08-29 /pmc/articles/PMC7520432/ /pubmed/33024815 http://dx.doi.org/10.1016/j.omto.2020.08.017 Text en © 2020. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Han, Rui
Nusbaum, Olivia
Chen, Xinyi
Zhu, Yong
Valeric Acid Suppresses Liver Cancer Development by Acting as a Novel HDAC Inhibitor
title Valeric Acid Suppresses Liver Cancer Development by Acting as a Novel HDAC Inhibitor
title_full Valeric Acid Suppresses Liver Cancer Development by Acting as a Novel HDAC Inhibitor
title_fullStr Valeric Acid Suppresses Liver Cancer Development by Acting as a Novel HDAC Inhibitor
title_full_unstemmed Valeric Acid Suppresses Liver Cancer Development by Acting as a Novel HDAC Inhibitor
title_short Valeric Acid Suppresses Liver Cancer Development by Acting as a Novel HDAC Inhibitor
title_sort valeric acid suppresses liver cancer development by acting as a novel hdac inhibitor
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520432/
https://www.ncbi.nlm.nih.gov/pubmed/33024815
http://dx.doi.org/10.1016/j.omto.2020.08.017
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