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缬草和戊酸可能通过介导表观遗传修饰来抑制乳腺癌细胞的生长。

Valerian and valeric acid inhibit growth of breast cancer cells possibly by mediating epigenetic modifications.

机构信息

Department of Environmental Health Sciences, Yale University School of Public Health, New Haven, CT, 06520, USA.

Department of Oncology and Hematology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China.

出版信息

Sci Rep. 2021 Jan 28;11(1):2519. doi: 10.1038/s41598-021-81620-x.

Abstract

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.

摘要

缬草根(Valeriana officinalis)是一种流行且广泛应用的草药补充剂,用于治疗睡眠障碍和失眠。由于昼夜节律因素与肿瘤发生之间存在联系,该草药改善睡眠功能的能力可能表明存在未被探索的抗肿瘤作用。特别值得关注的是缬草酸(缬草根的活性化学成分)与某些组蛋白去乙酰化酶(HDAC)抑制剂之间的结构相似性,这意味着缬草可能在表观遗传基因调控中发挥作用。在这项研究中,我们检验了假设,即与昼夜节律相关的草药缬草可以抑制乳腺癌细胞的生长,并探讨了缬草酸治疗相关的表观遗传变化。我们的研究结果表明,水缬草根提取物可降低乳腺癌细胞的生长。此外,在体外,缬草酸处理与乳腺癌细胞增殖、迁移、集落形成和 3D 形成的减少有关,其减少的程度呈剂量和时间依赖性,还与 HDAC 活性降低和全基因组 DNA 低甲基化有关。总的来说,这些发现表明,缬草酸可以通过介导表观遗传修饰,如抑制组蛋白去乙酰化酶和改变 DNA 甲基化,来降低乳腺癌细胞的增殖。本研究强调了缬草酸作为新型 HDAC 抑制剂和治疗乳腺癌的治疗剂的潜在用途。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81e5/7844014/011ab1ebf4e9/41598_2021_81620_Fig1_HTML.jpg

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