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 [C5H10O2]), 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.