Novel Aza-podophyllotoxin derivative induces oxidative phosphorylation and cell death via AMPK activation in triple-negative breast cancer
Menée à l'aide de lignées cellulaires de cancer du sein triple négatif et à l'aide de xénogreffes sur des modèles murins, cette étude met en évidence un mécanisme par lequel un nouveau dérivé de l'aza-podophyllotoxine induit la phosphorylation oxydative et la mort cellulaire via l'activation de la kinase AMPK
To circumvent Warburg effect, several clinical trials for different cancers are utilising a combinatorial approach using metabolic reprogramming and chemotherapeutic agents including metformin. The majority of these metabolic interventions work via indirectly activating AMP-activated protein kinase (AMPK) to alter cellular metabolism in favour of oxidative phosphorylation over aerobic glycolysis. The effect of these drugs is dependent on glycaemic and insulin conditions. Therefore, development of small molecules, which can activate AMPK, irrespective of the energy state, may be a better approach for triple-negative breast cancer (TNBC) treatment.