PMID- 33510252 OWN - NLM STAT- MEDLINE DCOM- 20210917 LR - 20240502 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 11 IP - 1 DP - 2021 Jan 28 TI - Valerian and valeric acid inhibit growth of breast cancer cells possibly by mediating epigenetic modifications. PG - 2519 LID - 10.1038/s41598-021-81620-x [doi] LID - 2519 AB - Valerian root (Valeriana officinalis) is a popular and widely available herbal supplement used to treat sleeping disorders and insomnia. The herb's ability to ameliorate sleep dysfunction may signify an unexplored anti-tumorigenic effect due to the connection between circadian factors and tumorigenesis. Of particular interest are the structural similarities shared between valeric acid, valerian's active chemical ingredient, and certain histone deacteylase (HDAC) inhibitors, which imply that valerian may play a role in epigenetic gene regulation. In this study, we tested the hypothesis that the circadian-related herb valerian can inhibit breast cancer cell growth and explored epigenetic changes associated with valeric acid treatment. Our results showed that aqueous valerian extract reduced growth of breast cancer cells. In addition, treatment of valeric acid was associated with decreased breast cancer cell proliferation, migration, colony formation and 3D formation in vitro in a dose- and time-dependent manner, as well as reduced HDAC activity and a global DNA hypomethylation. Overall, these findings demonstrate that valeric acid can decrease the breast cancer cell proliferation possibly by mediating epigenetic modifications such as the inhibition of histone deacetylases and alterations of DNA methylation. This study highlights a potential utility of valeric acid as a novel HDAC inhibitor and a therapeutic agent in the treatment of breast cancer. FAU - Shi, Fengqin AU - Shi F AD - Department of Environmental Health Sciences, Yale University School of Public Health, New Haven, CT, 06520, USA. AD - Department of Oncology and Hematology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China. FAU - Li, Ya AU - Li Y AD - Department of Environmental Health Sciences, Yale University School of Public Health, New Haven, CT, 06520, USA. AD - Department of Oncology and Hematology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China. FAU - Han, Rui AU - Han R AD - Department of Environmental Health Sciences, Yale University School of Public Health, New Haven, CT, 06520, USA. AD - Department of Oncology and Hematology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China. FAU - Fu, Alan AU - Fu A AD - Department of Environmental Health Sciences, Yale University School of Public Health, New Haven, CT, 06520, USA. FAU - Wang, Ronghua AU - Wang R AD - Department of Environmental Health Sciences, Yale University School of Public Health, New Haven, CT, 06520, USA. AD - Department of Oncology and Hematology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China. FAU - Nusbaum, Olivia AU - Nusbaum O AD - Department of Environmental Health Sciences, Yale University School of Public Health, New Haven, CT, 06520, USA. FAU - Qin, Qin AU - Qin Q AD - Department of Environmental Health Sciences, Yale University School of Public Health, New Haven, CT, 06520, USA. FAU - Chen, Xinyi AU - Chen X AD - Department of Oncology and Hematology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China. FAU - Hou, Li AU - Hou L AD - Department of Environmental Health Sciences, Yale University School of Public Health, New Haven, CT, 06520, USA. AD - Department of Oncology and Hematology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China. FAU - Zhu, Yong AU - Zhu Y AD - Department of Environmental Health Sciences, Yale University School of Public Health, New Haven, CT, 06520, USA. yong.zhu@yale.edu. LA - eng GR - R21 CA238100/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210128 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Antineoplastic Agents, Phytogenic) RN - 0 (Pentanoic Acids) RN - 0 (Plant Extracts) RN - GZK92PJM7B (n-pentanoic acid) SB - IM MH - Antineoplastic Agents, Phytogenic/chemistry/*pharmacology MH - Cell Line, Tumor MH - Cell Movement/drug effects/genetics MH - DNA Methylation/drug effects MH - Epigenesis, Genetic/*drug effects MH - Female MH - Gene Expression Regulation, Neoplastic/*drug effects MH - Gene Regulatory Networks MH - Humans MH - Pentanoic Acids/chemistry/*pharmacology MH - Plant Extracts/chemistry/pharmacology MH - Valerian/*chemistry PMC - PMC7844014 COIS- The authors declare no competing interests. EDAT- 2021/01/30 06:00 MHDA- 2021/09/18 06:00 PMCR- 2021/01/28 CRDT- 2021/01/29 05:50 PHST- 2020/09/28 00:00 [received] PHST- 2021/01/06 00:00 [accepted] PHST- 2021/01/29 05:50 [entrez] PHST- 2021/01/30 06:00 [pubmed] PHST- 2021/09/18 06:00 [medline] PHST- 2021/01/28 00:00 [pmc-release] AID - 10.1038/s41598-021-81620-x [pii] AID - 81620 [pii] AID - 10.1038/s41598-021-81620-x [doi] PST - epublish SO - Sci Rep. 2021 Jan 28;11(1):2519. doi: 10.1038/s41598-021-81620-x.