tetrocarcin-a and Triple-Negative-Breast-Neoplasms

Triple-negative breast cancers (TNBC) lack expression of three important receptors, and have limited treatment options. High expression of junctional adhesion molecule-A (JAM-A) has been linked with aggressive tumor phenotypes including TNBC. This study aimed to evaluate the bioactivity of a JAM-A-down-regulating compound, Tetrocarcin-A, in TNBC.. TNBC cell viability, colony formation and xenograft growth were examined in Tetrocarcin-A-treated HCC38 human cells, 4T1 mouse cells or patient-derived primary cells. Protein expression of cell fate signaling effectors was examined by immunoblotting (versus transient JAM-A gene silencing). Apoptotic pathways were investigated in parallel.. Tetrocarcin-A reduced TNBC cell viability in vitro and in an in ovo/semi-in vivo xenograft model. Tetrocarcin-A-induced JAM-A down-regulation and reduced ERK phosphorylation, followed by c-FOS phosphorylation on its transcription-regulating residue, which down-regulated several inhibitor of apoptosis (IAP) proteins and induced caspase-dependent intrinsic pathway of apoptosis.. Tetrocarcin-A merits further investigation as a novel anti-tumor agent in TNBC.

Topics: Aminoglycosides; Animals; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Chick Embryo; Chorioallantoic Membrane; Down-Regulation; Gene Silencing; Humans; Inhibitor of Apoptosis Proteins; Junctional Adhesion Molecule A; Mice; RNA, Small Interfering; Triple Negative Breast Neoplasms