Inhibitory Effects of Tangeretin, a Citrus Peel-Derived Flavonoid, on Breast Cancer Stem Cell Formation through Suppression of Stat3 Signaling
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 chromatograp...
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| Format: | Article |
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MDPI AG
2020-06-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/11/2599 |
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| author | Yu-Chan Ko Hack Sun Choi Ren Liu Ji-Hyang Kim Su-Lim Kim Bong-Sik Yun Dong-Sun Lee |
| author_facet | Yu-Chan Ko Hack Sun Choi Ren Liu Ji-Hyang Kim Su-Lim Kim Bong-Sik Yun Dong-Sun Lee |
| author_sort | Yu-Chan Ko |
| collection | DOAJ |
| description | 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<sup>+</sup>/CD24<sup>−</sup>) 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. |
| first_indexed | 2024-03-10T19:23:30Z |
| format | Article |
| id | doaj.art-1b36307b22dd4751a7dafb4b817da90e |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T19:23:30Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-1b36307b22dd4751a7dafb4b817da90e2023-11-20T02:43:56ZengMDPI AGMolecules1420-30492020-06-012511259910.3390/molecules25112599Inhibitory Effects of Tangeretin, a Citrus Peel-Derived Flavonoid, on Breast Cancer Stem Cell Formation through Suppression of Stat3 SignalingYu-Chan Ko0Hack Sun Choi1Ren Liu2Ji-Hyang Kim3Su-Lim Kim4Bong-Sik Yun5Dong-Sun Lee6Interdisciplinary Graduate Program in Advanced Convergence Technology and Science, Jeju National University, Jeju 63243, KoreaSubtropical/Tropical Organism Gene Bank, Jeju National University, Jeju 63243, KoreaInterdisciplinary Graduate Program in Advanced Convergence Technology and Science, Jeju National University, Jeju 63243, KoreaInterdisciplinary Graduate Program in Advanced Convergence Technology and Science, Jeju National University, Jeju 63243, KoreaInterdisciplinary Graduate Program in Advanced Convergence Technology and Science, Jeju National University, Jeju 63243, KoreaDivision of Biotechnology, College of Environmental and Bioresource Sciences, Jeonbuk National University, Gobong-ro 79, Iksan 54596, KoreaInterdisciplinary Graduate Program in Advanced Convergence Technology and Science, Jeju National University, Jeju 63243, KoreaBreast 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<sup>+</sup>/CD24<sup>−</sup>) 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.https://www.mdpi.com/1420-3049/25/11/2599tangeretincancer stem cellsStat3citrusCD44<sup>+</sup>/CD24<sup>−</sup>phytochemicals |
| spellingShingle | Yu-Chan Ko Hack Sun Choi Ren Liu Ji-Hyang Kim Su-Lim Kim Bong-Sik Yun Dong-Sun Lee Inhibitory Effects of Tangeretin, a Citrus Peel-Derived Flavonoid, on Breast Cancer Stem Cell Formation through Suppression of Stat3 Signaling Molecules tangeretin cancer stem cells Stat3 citrus CD44<sup>+</sup>/CD24<sup>−</sup> phytochemicals |
| title | Inhibitory Effects of Tangeretin, a Citrus Peel-Derived Flavonoid, on Breast Cancer Stem Cell Formation through Suppression of Stat3 Signaling |
| title_full | Inhibitory Effects of Tangeretin, a Citrus Peel-Derived Flavonoid, on Breast Cancer Stem Cell Formation through Suppression of Stat3 Signaling |
| title_fullStr | Inhibitory Effects of Tangeretin, a Citrus Peel-Derived Flavonoid, on Breast Cancer Stem Cell Formation through Suppression of Stat3 Signaling |
| title_full_unstemmed | Inhibitory Effects of Tangeretin, a Citrus Peel-Derived Flavonoid, on Breast Cancer Stem Cell Formation through Suppression of Stat3 Signaling |
| title_short | Inhibitory Effects of Tangeretin, a Citrus Peel-Derived Flavonoid, on Breast Cancer Stem Cell Formation through Suppression of Stat3 Signaling |
| title_sort | inhibitory effects of tangeretin a citrus peel derived flavonoid on breast cancer stem cell formation through suppression of stat3 signaling |
| topic | tangeretin cancer stem cells Stat3 citrus CD44<sup>+</sup>/CD24<sup>−</sup> phytochemicals |
| url | https://www.mdpi.com/1420-3049/25/11/2599 |
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