Machilin D, a Lignin Derived from Saururus chinensis, Suppresses Breast Cancer Stem Cells and Inhibits NF-κB Signaling

• Published in: Biomolecules (Basel, Switzerland) Switzerland), 2020-02, Vol.10 (2), p.245
• Main Authors: Zhen, Xing, Choi, Hack Sun, Kim, Ji-Hyang, Kim, Su-Lim, Liu, Ren, Yun, Bong-Sik, Lee, Dong-Sun
• Format: Article
• Language: English
• Subjects: Active Transport, Cell Nucleus; Aldehyde Dehydrogenase 1 Family - metabolism; Animals; breast cancer stem cells (bcscs); Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; CD24 Antigen - metabolism; Cell Line, Tumor; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Female; Gene Expression Regulation, Neoplastic; Humans; Hyaluronan Receptors - metabolism; Interleukin-6 - metabolism; Interleukin-8 - metabolism; Lignans - pharmacology; machilin d; Magnetic Resonance Spectroscopy; mammospheres; Mass Spectrometry; MCF-7 Cells; Mice; Mice, Nude; Neoplasm Transplantation; Neoplastic Stem Cells - drug effects; Neoplastic Stem Cells - metabolism; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; nf-κb; Plant Extracts - chemistry; Powders; Saururaceae - chemistry; Signal Transduction - drug effects
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom10020245

Cancer stem cells are responsible for breast cancer initiation, metastasis, and relapse. Targeting breast cancer stem cells (BCSCs) using phytochemicals is a good strategy for the treatment of cancer. A silica gel, a reversed-phase C18 column (ODS), a Sephadex LH-20 gel, thin layer chromatography, and high-performance liquid chromatography (HPLC) were used for compound isolation from Saururus chinensis extracts. The isolated compound was identified as machilin D by mass spectrometry and nuclear magnetic resonance (NMR). Machilin D inhibited the growth and mammosphere formation of breast cancer cells and inhibited tumor growth in a xenograft mouse model. Machilin D reduced the proportions of CD44 /CD24 and aldehyde dehydrogenase 1 (ALDH1)-positive cells. Furthermore, this compound reduced the nuclear localization of the NF-κB protein and decreased the IL-6 and IL-8 secretion in mammospheres. These results suggest that machilin D blocks IL-6 and IL-8 signaling and induces CSC death and thus may be a potential agent targeting BCSCs.