Novel TGF-β1 inhibitor antagonizes TGF-β1-induced epithelial-mesenchymal transition in human A549 lung cancer cells

Journal of Cellular Biochemistry
Ji-Hoon JeongKyung-Chul Choi

Abstract

Transforming growth factor β1 (TGF-β1), a multifunctional cytokine, is known to promote tumor invasion and metastasis and induce epithelial-mesenchymal transition (EMT) in various cancer cells. Inhibition of TGF-β1 signaling is a new strategy for cancer therapy. Most cancer cells display altered or nonfunctional TGF-β1 signaling; hence, TGF-β1 inhibitors exert limited effects on these cells. Recent studies have suggested that developing a TGF-β1 inhibitor from natural compounds is a key step to create novel therapeutic agents. This study aimed to develop a new anti-TGF-β1 therapy for cancer. We found an improved analog of chalcones, compound 67, and investigated its effects in vitro. We demonstrated the inhibitory role of compound 67 through migration and invasion assays on TGF-β1-induced EMT of human A549 lung cancer cells. Compound 67 inhibited TGF-β1-induced smad2 phosphorylation, suppressed TGF-β1-induced EMT markers, matrix metalloproteinase-2 (MMP-2) and MMP-9, and inhibited migration and invasion of A549 cells. The study results showed that compound 67 is useful to prevent tumor growth and metastasis.

References

Jan 1, 1990·Annals of the New York Academy of Sciences·A B RobertsM B Sporn
Aug 19, 2003·Nature Reviews. Molecular Cell Biology·Stefan GrünertHartmut Beug
Nov 19, 2003·Mechanisms of Development·David Shook, Ray Keller
Jul 16, 2005·Experimental Lung Research·Subhadeep Chakrabarti, Kamala D Patel
Sep 24, 2005·Journal of Cell Science·Derek C Radisky
Dec 7, 2007·Laboratory Investigation; a Journal of Technical Methods and Pathology·Karolina A RygielJohn A Kirby
Feb 5, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Haiying YuOliver Eickelberg
Sep 6, 2008·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Yi-Chin FongChih-Hsin Tang
Dec 1, 2009·Cell·Jean Paul ThieryM Angela Nieto
Jan 19, 2010·Proceedings of the National Academy of Sciences of the United States of America·Daxing XieJer-Tsong Hsieh
Mar 8, 2011·American Journal of Physiology. Lung Cellular and Molecular Physiology·Ricardo E PerezIkechukwu I Ekekezie
Apr 24, 2013·Bioorganic & Medicinal Chemistry Letters·Seok-Ho KimYounghwa Na
Aug 27, 2013·Lancet·Martin ReckKlaus F Rabe
Jan 9, 2014·CA: a Cancer Journal for Clinicians·Rebecca SiegelAhmedin Jemal
Oct 26, 2016·Bioorganic & Medicinal Chemistry·Kyung-Hwa JeonYounghwa Na

❮ Previous
Next ❯

Citations

Aug 6, 2019·Clinical and Experimental Pharmacology & Physiology·Siyao WangShun Xu
Jul 3, 2021·Biomolecules·Yang OuyangQi Wu

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

Cell Migration in Cancer and Metastasis

Migration of cancer cells into surrounding tissue and the vasculature is an initial step in tumor metastasis. Discover the latest research on cell migration in cancer and metastasis here.