Stephanie P Totten, Young Kyuen Im, Eduardo Cepeda Cañedo, Ouafa Najyb, Alice Nguyen, Steven Hébert, Ryuhjin Ahn, Kyle Lewis, Benjamin Lebeau, Rachel La Selva, Valérie Sabourin, Constanza Martínez, Paul Savage, Hellen Kuasne, Daina Avizonis, Nancy Santos Martínez, Catherine Chabot, Adriana Aguilar-Mahecha, Marie-Line Goulet, Matthew Dankner, Michael Witcher, Kevin Petrecca, Mark Basik, Michael Pollak, Ivan Topisirovic, Rongtuan Lin, Peter M Siegel, Claudia L Kleinman, Morag Park, Julie St-Pierre, Josie Ursini-Siegel
Bioenergetic perturbations driving neoplastic growth increase the production of reactive oxygen species (ROS), requiring a compensatory increase in ROS scavengers to limit oxidative stress. Intervention strategies that simultaneously induce energetic and oxidative stress therefore have therapeutic potential. Phenformin is a mitochondrial complex I inhibitor that induces bioenergetic stress. We now demonstrate that inflammatory mediators, including IFNγ and polyIC, potentiate the cytotoxicity of phenformin by inducing a parallel increase in oxidative stress through STAT1-dependent mechanisms...
June 3, 2021: Nature Communications