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Trichothecin Inhibits Cancer-Related Features in Colorectal Cancer Development by Targeting STAT3
Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that contributes to cancer progression through multiple processes of cancer development, which makes it an attractive target for cancer therapy. The IL-6/STAT3 pathway is associated with an advanced stage in colorec...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7287781/ https://www.ncbi.nlm.nih.gov/pubmed/32422984 http://dx.doi.org/10.3390/molecules25102306 |
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author | Qi, Xin Li, Meng Zhang, Xiao-min Dai, Xiu-fen Cui, Jian Li, De-hai Gu, Qian-qun Lv, Zhi-hua Li, Jing |
author_facet | Qi, Xin Li, Meng Zhang, Xiao-min Dai, Xiu-fen Cui, Jian Li, De-hai Gu, Qian-qun Lv, Zhi-hua Li, Jing |
author_sort | Qi, Xin |
collection | PubMed |
description | Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that contributes to cancer progression through multiple processes of cancer development, which makes it an attractive target for cancer therapy. The IL-6/STAT3 pathway is associated with an advanced stage in colorectal cancer patients. In this study, we identified trichothecin (TCN) as a novel STAT3 inhibitor. TCN was found to bind to the SH2 domain of STAT3 and inhibit STAT3 activation and dimerization, thereby blocking STAT3 nuclear translocation and transcriptional activity. TCN did not affect phosphorylation levels of STAT1. TCN significantly inhibited cell growth, arrested cell cycle at the G0/G1 phase, and induced apoptosis in HCT 116 cells. In addition, the capacities of colony formation, migration, and invasion of HCT 116 cells were impaired upon exposure to TCN with or without IL-6 stimulation. In addition, TCN treatment abolished the tube formation of HUVEC cells in vitro. Taken together, these results highlight that TCN inhibits various cancer-related features in colorectal cancer development in vitro by targeting STAT3, indicating that TCN is a promising STAT3 inhibitor that deserves further exploration in the future. |
format | Online Article Text |
id | pubmed-7287781 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-72877812020-06-15 Trichothecin Inhibits Cancer-Related Features in Colorectal Cancer Development by Targeting STAT3 Qi, Xin Li, Meng Zhang, Xiao-min Dai, Xiu-fen Cui, Jian Li, De-hai Gu, Qian-qun Lv, Zhi-hua Li, Jing Molecules Article Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that contributes to cancer progression through multiple processes of cancer development, which makes it an attractive target for cancer therapy. The IL-6/STAT3 pathway is associated with an advanced stage in colorectal cancer patients. In this study, we identified trichothecin (TCN) as a novel STAT3 inhibitor. TCN was found to bind to the SH2 domain of STAT3 and inhibit STAT3 activation and dimerization, thereby blocking STAT3 nuclear translocation and transcriptional activity. TCN did not affect phosphorylation levels of STAT1. TCN significantly inhibited cell growth, arrested cell cycle at the G0/G1 phase, and induced apoptosis in HCT 116 cells. In addition, the capacities of colony formation, migration, and invasion of HCT 116 cells were impaired upon exposure to TCN with or without IL-6 stimulation. In addition, TCN treatment abolished the tube formation of HUVEC cells in vitro. Taken together, these results highlight that TCN inhibits various cancer-related features in colorectal cancer development in vitro by targeting STAT3, indicating that TCN is a promising STAT3 inhibitor that deserves further exploration in the future. MDPI 2020-05-14 /pmc/articles/PMC7287781/ /pubmed/32422984 http://dx.doi.org/10.3390/molecules25102306 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Qi, Xin Li, Meng Zhang, Xiao-min Dai, Xiu-fen Cui, Jian Li, De-hai Gu, Qian-qun Lv, Zhi-hua Li, Jing Trichothecin Inhibits Cancer-Related Features in Colorectal Cancer Development by Targeting STAT3 |
title | Trichothecin Inhibits Cancer-Related Features in Colorectal Cancer Development by Targeting STAT3 |
title_full | Trichothecin Inhibits Cancer-Related Features in Colorectal Cancer Development by Targeting STAT3 |
title_fullStr | Trichothecin Inhibits Cancer-Related Features in Colorectal Cancer Development by Targeting STAT3 |
title_full_unstemmed | Trichothecin Inhibits Cancer-Related Features in Colorectal Cancer Development by Targeting STAT3 |
title_short | Trichothecin Inhibits Cancer-Related Features in Colorectal Cancer Development by Targeting STAT3 |
title_sort | trichothecin inhibits cancer-related features in colorectal cancer development by targeting stat3 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7287781/ https://www.ncbi.nlm.nih.gov/pubmed/32422984 http://dx.doi.org/10.3390/molecules25102306 |
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