Inhibitory Impact of the Amino Benzoic Derivative DAB-2-28 on the Process of Epithelial-Mesenchymal Transition in Human Breast Cancer Cells

Fortin, Louis Guillaume; Girouard, Julie; Oufqir, Yassine; Paquin, Alexis; Cloutier, Francis; Plante, Isabelle ORCID: https://orcid.org/0000-0003-2080-6450; Bérubé, Geneviève et Reyes-Moreno, Carlos (2025). Inhibitory Impact of the Amino Benzoic Derivative DAB-2-28 on the Process of Epithelial-Mesenchymal Transition in Human Breast Cancer Cells Molecules , vol. 30 , nº 15:3284. pp. 1-20. DOI: 10.3390/molecules30153284.

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Résumé

Macrophage-mediated inflammation is known to be involved in the epithelial-mesenchymal transition (EMT) of various types of cancer. This makes macrophage-derived inflammatory factors prime targets for the development of new treatments. This study uncovers the therapeutic potential and action mechanism of DAB-2-28, a small-molecule derived from para-aminobenzoic acid, in the treatment of breast cancer. The luminal MCF-7 and the triple-negative MDA-MB-231 cancer cell lines used in this study represent, respectively, breast cancers in which the differentiation states are related to the epithelial phenotype of the mammary gland and breast cancers expressing a highly aggressive mesenchymal phenotype. In MCF-7 cells, soluble factors from macrophage-conditioned media (CM-M & Oslash;) induce a characteristic morphology of mesenchymal cells with an upregulated expression of Snail1, a mesenchymal marker, as opposed to a decrease in the expression of E-cadherin, an epithelial marker. DAB-2-28 does not affect the differential expression of Snail1 and E-cadherin in response to CM-M & Oslash;, but negatively impacts other hallmarks of EMT by decreasing invasion and migration capacities, in addition to MMP9 expression and gelatinase activity, in both MCF-7 and MDA-MB-231 cells. Moreover, DAB-2-28 inhibits the phosphorylation of key pro-EMT transcriptional factors, such as NF kappa B, STAT3, SMAD2, CREB, and/or AKT proteins, in breast cancer cells exposed to different EMT inducers. Overall, our study provides evidence suggesting that inhibition of EMT initiation or maintenance is a key mechanism by which DAB-2-28 can exert anti-tumoral effects in breast cancer cells.

Type de document:	Article
Informations complémentaires:	This research was funded by the Cancer Research Society (CRS: number 22471) and the Canadian Institutes of Health Research (CIHR; number 392334). This work was also sponsored by a grant from Aligo Innovation (number 150923) and the “Ministère de l’Économie et de l’Innovation”, Québec Government, to C. Reyes-Moreno and G. Bérubé; and a grant from the Natural Sciences and Engineering Research Council of Canada (NSERC), to I.P. (number RGPIN-2020-05726)
Mots-clés libres:	Inflammation; luminal breast cancer; macrophages; para-aminobenzoic acid (PABA); small molecules; triple-negative breast cancer
Centre:	Centre INRS-Institut Armand Frappier
Date de dépôt:	04 juin 2026 15:10
Dernière modification:	04 juin 2026 15:10
URI:	https://espace.inrs.ca/id/eprint/16636

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