pepstatin and Triple-Negative-Breast-Neoplasms

Triple-negative breast cancers (TNBCs) are more aggressive than other breast cancer (BC) subtypes and lack effective therapeutic options. Unraveling marker events of TNBCs may provide new directions for development of strategies for targeted TNBC therapy. Herein, we reported that Annexin A1 (AnxA1) and Cathepsin D (CatD) are highly expressed in MDA-MB-231 (TNBC lineage), compared to MCF-10A and MCF-7. Since the proposed concept was that CatD has protumorigenic activity associated with its ability to cleave AnxA1 (generating a 35.5 KDa fragment), we investigated this mechanism more deeply using the inhibitor of CatD, Pepstatin A (PepA). Fourier Transform Infrared (FTIR) spectroscopy demonstrated that PepA inhibits CatD activity by occupying its active site; the OH bond from PepA interacts with a CO bond from carboxylic acids of CatD catalytic aspartate dyad, favoring the deprotonation of Asp

Topics: Annexin A1; Apoptosis; Autophagy; Catalytic Domain; Cathepsin D; Cell Lineage; Cell Movement; Cell Proliferation; Female; Gene Expression Regulation, Neoplastic; Humans; MCF-7 Cells; Molecular Docking Simulation; Neoplasm Invasiveness; Pepstatins; Spectroscopy, Fourier Transform Infrared; Triple Negative Breast Neoplasms