Coumarin Derivatives Exert Anti-Lung Cancer Activity by Inhibition of Epithelial-Mesenchymal Transition and Migration in A549 Cells.

Autor: de Araújo RSA; Laboratory of Synthesis and Drug Delivery, Department of Biological Sciences, State University of Paraiba, João Pessoa 58429-500, PB, Brazil.; Laboratoire d'Innovation Thérapeutique, UMR 7200, Labex Medalis, CNRS, Université de Strasbourg, Faculté de Pharmacie, 74 route du Rhin, BP 60024, 67401 Illkirch, France., Carmo JODS; Institute of Biological and Health Sciences, Federal University of Alagoas, Maceio 57072-900, AL, Brazil., de Omena Silva SL; Institute of Biological and Health Sciences, Federal University of Alagoas, Maceio 57072-900, AL, Brazil., Costa da Silva CRA; Institute of Biological and Health Sciences, Federal University of Alagoas, Maceio 57072-900, AL, Brazil., Souza TPM; Institute of Biological and Health Sciences, Federal University of Alagoas, Maceio 57072-900, AL, Brazil., Mélo NB; Laboratory of Synthesis and Drug Delivery, Department of Biological Sciences, State University of Paraiba, João Pessoa 58429-500, PB, Brazil., Bourguignon JJ; Laboratoire d'Innovation Thérapeutique, UMR 7200, Labex Medalis, CNRS, Université de Strasbourg, Faculté de Pharmacie, 74 route du Rhin, BP 60024, 67401 Illkirch, France., Schmitt M; Laboratoire d'Innovation Thérapeutique, UMR 7200, Labex Medalis, CNRS, Université de Strasbourg, Faculté de Pharmacie, 74 route du Rhin, BP 60024, 67401 Illkirch, France., Aquino TM; Research Group on Therapeutic Strategies-GPET, Institute of Chemistry and Biotechnology, Federal University of Alagoas, Maceio 57072-900, AL, Brazil., Rodarte RS; Institute of Biological and Health Sciences, Federal University of Alagoas, Maceio 57072-900, AL, Brazil., Moura RO; Laboratory of Synthesis and Drug Delivery, Department of Biological Sciences, State University of Paraiba, João Pessoa 58429-500, PB, Brazil., Barbosa Filho JM; Post-Graduate Program in Natural and Synthetic Bioactive Products, Federal University of Paraíba, João Pessoa 58051-900, PB, Brazil., Barreto E; Institute of Biological and Health Sciences, Federal University of Alagoas, Maceio 57072-900, AL, Brazil., Mendonça-Junior FJB; Laboratory of Synthesis and Drug Delivery, Department of Biological Sciences, State University of Paraiba, João Pessoa 58429-500, PB, Brazil.; Post-Graduate Program in Natural and Synthetic Bioactive Products, Federal University of Paraíba, João Pessoa 58051-900, PB, Brazil.
Jazyk: angličtina
Zdroj: Pharmaceuticals (Basel, Switzerland) [Pharmaceuticals (Basel)] 2022 Jan 17; Vol. 15 (1). Date of Electronic Publication: 2022 Jan 17.
DOI: 10.3390/ph15010104
Abstrakt: A series of coumarin derivatives and isosteres were synthesized from the reaction of triflic intermediates with phenylboronic acids, terminal alkynes, and organozinc compounds through palladium -catalyzed cross-coupling reactions. The in vitro cytotoxic effect of the compounds was evaluated against two non-small cell lung carcinoma (NSCLC) cell lines (A-549 and H2170) and a normal cell line (NIH-3T3) using cisplatin as a reference drug. Additionally, the effects of the most promising coumarin derivative ( 9f ) in reversing the epithelial-to-mesenchymal transition (EMT) in IL-1β-stimulated A549 cells and in inhibiting the EMT-associated migratory ability in A549 cells were also evaluated. 9f had the greatest cytotoxic effect (CC 50 = 7.1 ± 0.8 and 3.3 ± 0.5 μM, respectively against A549 and H2170 cells) and CC 50 value of 25.8 µM for NIH-3T3 cells. 9f inhibited the IL-1β-induced EMT in epithelial cells by inhibiting the F-actin reorganization, attenuating changes in the actin cytoskeleton reorganization, and downregulating vimentin in A549 cells stimulated by IL-1β. Treatment of A549 cells with 9f at 7 µM for 24 h significantly reduced the migration of IL-1β-stimulated cells, which is a phenomenon confirmed by qualitative assessment of the wound closure. Taken together, our findings suggest that coumarin derivatives, especially compound 9f , may become a promising candidate for lung cancer therapy, especially in lung cancer promoted by NSCLC cell lines.
Databáze: MEDLINE
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