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

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.

Effects of Dietary Coated Lysozyme on the Growth Performance, Antioxidant Activity, Immunity and Gut Health of Weaned Piglets

“…Short-chain fatty acids are metabolites of intestinal anaerobic microorganisms that can not only provide energy for intestinal epithelial cells but also play a role in regulating the intestinal flora [ 46 , 47 ]. In addition, valeric acid has the effect of inhibiting the growth of breast cancer cells and protecting dopaminergic neurons [ 48 , 49 ]. A large number of intestinal bacteria form a complex microbial system with various functions, such as digestion, absorption, metabolism, and immunity [ 50 , 51 ].…”

Analysis of Intestinal Short-Chain Fatty Acid Metabolism Profile After Probiotics and GLP-1 Treatment for Type 2 Diabetes Mellitus

“…Han et al found that Valeric acid has a broad spectrum of antitumor activities, showing particularly high cytotoxicity to liver cancer in cell proliferation, colony formation, wound healing, cell invasion and 3D spherogenesis (27). Shi et al found that valerate may reduce breast cancer cell proliferation by mediating epigenetic modifications, such as inhibiting histone deacetylase and altering DNA methylation (28). Similarly, Valeric acid has the effect of alleviating intestinal radiation injury and protecting neuronal injury, and also has the regulation function of neurotransmitter (29)(30)(31).…”

“…Shi et al. found that valerate may reduce breast cancer cell proliferation by mediating epigenetic modifications, such as inhibiting histone deacetylase and altering DNA methylation ( 28 ). Similarly, Valeric acid has the effect of alleviating intestinal radiation injury and protecting neuronal injury, and also has the regulation function of neurotransmitter ( 29 – 31 ).…”

"Valeriana officinalis" – a review

“…The authors also suggest the potential effectiveness of valerian acid as an HDAC inhibitor. 38 Hellum et al in their work on in vitro cells, they presented the effect of valerian on mechanism-based inhibition of CYP2D6 activity. The study demonstrated the action of valerian components as inhibitors on CYP2D6 enzyme activity.…”