Caudatin Isolated from Cynanchum auriculatum Inhibits Breast Cancer Stem Cell Formation via a GR/YAP Signaling
Interdisciplinary Graduate Program in Advanced Convergence Technology and Science, Jeju National University, Jeju 63243, Korea
Subtropical/Tropical Organism Gene Bank, Jeju National University, Jeju 63243, Korea
Division of Biotechnology, College of Environmental and Bioresource Sciences, Jeonbuk National University, Gobong-ro 79, Iksan 54596, Korea
Practical Translational Research Center, Jeju National University, Jeju 63243, Korea
Faculty of Biotechnology, College of Applied Life Sciences, Jeju National University, SARI, Jeju 63243, Korea
Author to whom correspondence should be addressed.
Xing Zhen and Hack Sun Choi contributed equally to this work.
Biomolecules 2020, 10(6), 925; https://doi.org/10.3390/biom10060925
Received: 6 May 2020 / Revised: 6 June 2020 / Accepted: 15 June 2020 / Published: 18 June 2020
(This article belongs to the Special Issue Bioactive Lipids in Inflammation, Diabetes and Cancer)
In the complex tumor microenvironment, cancer stem cells (CSCs), a rare population of cells, are responsible for malignant tumor initiation, metastasis, drug resistance and recurrence. Controlling breast CSCs (BCSCs) using natural compounds is a novel potential therapeutic strategy for clinical cancer treatment. In this study, a mammosphere assay-guided isolation protocol including silica gel, a C18 column, gel filtration, and high-pressure liquid chromatography was used to isolate an inhibitory compound from Cynanchum auriculatum extracts. The isolated inhibitory compound was identified as caudatin. Caudatin inhibited breast cancer cell proliferation, mammosphere formation and tumor growth. Caudatin decreased the CD44+/CD24− and aldehyde dehydrogenase+ cell proportions and the levels of c-Myc, Oct4, Sox2, and CD44. Caudatin induced ubiquitin (Ub)-dependent glucocorticoid receptor (GR) degradation and blocked subsequent Yes-associated protein (YAP) nuclear accumulation and target gene transcription signals in BCSCs. These results show that the GR/YAP signaling pathway regulates BCSC formation and that caudatin may be a potential chemopreventive agent that targets breast cancer cells and CSCs.