A New TGF-β1 Inhibitor, CTI-82, Antagonizes Epithelial-Mesenchymal Transition through Inhibition of Phospho-SMAD2/3 and Phospho-ERK
| Autor: | Younghwa Na, Ji-Hye Song, Gi-Jun Sung, Hayeon Park, Kyung-Chul Choi, Minseok Jeong, Ji-Hoon Jeong, Sungmin Kwak, Hyunhee Kim, Seung-Ho Park |
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| Rok vydání: | 2020 |
| Předmět: |
Tumor microenvironment
General Immunology and Microbiology EMT Cancer chalcone Cell migration Biology medicine.disease migration invasion General Biochemistry Genetics and Molecular Biology Article TGF-β1 inhibitor Metastasis lcsh:Biology (General) TGF-β1 Cancer cell Cancer research medicine Epithelial–mesenchymal transition Signal transduction General Agricultural and Biological Sciences lcsh:QH301-705.5 Transforming growth factor |
| Zdroj: | Biology Biology, Vol 9, Iss 143, p 143 (2020) Volume 9 Issue 7 |
| ISSN: | 2079-7737 |
| Popis: | Transforming growth factor-&beta 1 (TGF-&beta 1) is highly expressed in the tumor microenvironment and known to play a multifunctional role in cancer progression. In addition, TGF-&beta 1 promotes metastasis by inducing epithelial&ndash mesenchymal transition (EMT) in a variety of tumors. Thus, inhibition of TGF-&beta 1 is considered an important strategy in the treatment of cancer. In most tumors, TGF-&beta 1 signal transduction exhibits modified or non-functional characteristics, and TGF-&beta 1 inhibitors have various inhibitory effects on cancer cells. Currently, many studies are being conducted to develop TGF-&beta 1 inhibitors from non-toxic natural compounds. We aimed to develop a new TGF-&beta 1 inhibitor to suppress EMT in cancer cells. As a result, improved chalcone-like chain CTI-82 was identified, and its effect was confirmed in vitro. We showed that CTI-82 blocked TGF-&beta 1-induced EMT by inhibiting the cell migration and metastasis of A549 lung cancer cells. In addition, CTI-82 reduced the TGF-&beta 1-induced phosphorylation of SMAD2/3 and inhibited the expression of various EMT markers. Our results suggest that CTI-82 inhibits tumor growth, migration, and metastasis. |
| Databáze: | OpenAIRE |
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