Mariana Gallo, Elena Ferrari, Anna Terrazzan, Federica Brugnoli, Alberto Spisni, Cristian Taccioli, Gianluca Aguiari, Alessandro Trentini, Stefano Volinia, Jeffrey W Keillor, Carlo M Bergamini, Nicoletta Bianchi, Thelma A Pertinhez
Transglutaminase 2 (TG2), mediating post-translational modifications of multiple intracellular enzymes, is involved in the pathogenesis and progression of cancer. We used 1 H-NMR metabolomics to study the effects of AA9, a novel TG2 inhibitor, on two breast cancer cell lines with distinct phenotypes, MCF-7 and MDA-MB-231. AA9 can promote apoptosis in both cell lines, but it is particularly effective in MD-MB-231, inhibiting transamidation reactions and decreasing cell migration and invasiveness. This metabolomics study provides evidence of a major effect of AA9 on MDA-MB-231 cells, impacting glutamate and aspartate metabolism, rather than on MCF-7 cells, characterized by choline and O-phosphocholine decrease...
August 19, 2023: FEBS Journal