Anticancer efficiency of cycloartane triterpenoid derivatives isolated from Cimicifuga yunnanensis Hsiao on triple-negative breast cancer cells

Xiao Li,1,2 Wei Wang,1 Yi Fan,1 Yue Wei,1 Li-Qin Yu,1 Ji-Fu Wei,3 Yi-Fen Wang2 1Biotechnology Developing Center of Henan Academy of Sciences, Henan Academy of Sciences, Zhengzhou 450002, Henan, People’s Republic of China; 2State Key Laboratory of Photochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, People’s Republic of China; 3Research Division of Clinical Pharmacology, The First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, People’s Republic of China Background: The roots and rhizomes of Cimicifuga yunnanensis Hsiao are commonly used as anti-inflammatory, antipyretic, and analgesic remedies and detoxification agents in traditional Chinese medicine (TCM). Although C. yunnanensis has been considered as supplementary medicine for several disorders, the antitumor effect of this herb and its key components has not been explored.Materials and methods: The rhizomes of C. yunnanensis were isolated by chromatographic techniques. Structures of isolated compounds were identified based on spectroscopic methods and comparison with published data. The in vitro anticancer activities of purified components were also performed by MTT experiments. The in vivo anticancer activities were examined by subcutaneous tumor model or a breast cancer liver metastasis model.Results: In this study, we aimed to identify and characterize the effective antitumor components from the rhizomes of C. yunnanensis. By bioassay-guided fractionation techniques and chemical characterization, 12 cycloartane triterpenes and four chromones were isolated, among them, 11 compounds were identified in this genus at first. The identified two compounds showed dramatic inhibitory activities against breast cancer cells: compound 4 (23-epi-26-deoxyactein) and compound 13 (cimigenol). Then, we examined the antitumor effect of these two selective candidate chemicals on triple-negative breast cancer (TNBC) cells in vivo and found that they could reduce tumor growth in subcutaneous tumor model or breast cancer liver metastasis model.Conclusion: These results suggested that the selective compounds isolated from C. yunnanensis Hsiao could be the promising new agents for TNBC treatment. Keywords: Cimicifuga, Cimicifuga yunnanensis, cycloartane triterpenoids, anticancer activity, triple-negative breast cancer, breast cancer liver metastasi