Inhibitory Impact of the Amino Benzoic Derivative DAB-2-28 on the Process of Epithelial-Mesenchymal Transition in Human Breast Cancer Cells
Bibliographic record
Abstract
Macrophage-mediated inflammation is proposed to be involved in the epithelial-mesenchymal transition (EMT) of different types of cancers. This makes macrophage-derived inflammatory factors a prime target for developing new treatments. This study aims to demonstrate the therapeutic potential and mechanism of action of DAB-2-28, a novel small molecule derived from 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, a breast cancer whose differentiation state is related to the epithelial phenotype of the mammary gland, and a breast cancer expressing a highly aggressive mesenchymal phenotype. In MCF-7 cells, soluble factors from macrophage-conditioned media (MØ-CM) induce a characteristic morphology of mesenchymal cells with an increase in the expression of Snail1, a mesenchymal marker, opposed to a decrease in the expression of E-cadherin, an epithelial marker. Although our studies demonstrated that DAB-2-28 does not affect the differential expression of Snail1 and E-cadherin, DAB-2-28 negatively regulates the different responses of MCF-7 cells to MØ-CM by decreasing a) clonogenic growth; b) invasion and migration capacities; c) MMP9 expression and gelatinase activity; and d) NFkB, STAT3, AKT, and SMAD2 protein phosphorylation. Moreover, differential expression of Snail1 and E-cadherin in MCF-7 cells was also induced by the cytokines TNFa and TGFb1, alone or in combination, and the StemXvivo® EMT Inducing Media reagent. DAB-2-28 affects the response of MCF-7 cells to these various EMT inducers by inhibiting the phosphorylation of NFkB, SMAD2 and/or CREB proteins. Finally, DAB-2-28 also decreases the macrophage- and cytokine-induced invasion and migration capacities of MDA-MB-231 cells, probably via an inhibition of MMP9 activity and the phosphorylation of NFkB, STAT3, AKT, SMAD2, and CREB proteins. We propose that the ability of DAB-2-28 to prevent cancer cells from acquiring EMT-related protumor properties could be exploited in a clinical setting to block disease progression to a metastatic form and thus improve the survival rate of breast cancer patients.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".