Inhibitory Effects of Tangeretin, a Citrus Peel-Derived Flavonoid, on Breast Cancer Stem Cell Formation through Suppression of Stat3 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.
Yu-Chan Ko and Hack Sun Choi contributed equally to this work.
Academic Editor: H.P. Vasantha Rupasinghe
Molecules 2020, 25(11), 2599; https://doi.org/10.3390/molecules25112599
Received: 20 May 2020 / Revised: 1 June 2020 / Accepted: 2 June 2020 / Published: 3 June 2020
(This article belongs to the Special Issue Flavonoids and Their Disease Prevention and Treatment Potential)
Breast cancer stem cells (BCSCs) are responsible for tumor chemoresistance and recurrence. Targeting CSCs using natural compounds is a novel approach for cancer therapy. A CSC-inhibiting compound was purified from citrus extracts using silica gel, gel filtration and high-pressure liquid chromatography. The purified compound was identified as tangeretin by using nuclear magnetic resonance (NMR). Tangeretin inhibited cell proliferation, CSC formation and tumor growth, and modestly induced apoptosis in CSCs. The frequency of a subpopulation with a CSC phenotype (CD44+/CD24−) was reduced by tangeretin. Tangeretin reduced the total level and phosphorylated nuclear level of signal transducer and activator of transcription 3 (Stat3). Our results in this study show that tangeretin inhibits the Stat3 signaling pathway and induces CSC death, indicating that tangeretin may be a potential natural compound that targets breast cancer cells and CSCs.