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Additional file 4: Figure S4. of Targeting mitochondrial complex I using BAY 87-2243 reduces melanoma tumor growth

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posted on 24.10.2019, 12:52 by Laura Schöckel, Andrea Glasauer, Farhan Basit, Katharina Bitschar, Hoa Truong, Gerrit Erdmann, Carolyn Algire, Andrea Hägebarth, Peter Willems, Charlotte Kopitz, Werner Koopman, Mélanie Héroult
Melanoma cells are sensitive to BAY 87-2243-mediated Complex I inhibition by undergoing an energy crisis and ROS-mediated cell death. Under limiting glucose conditions (5 mM), the mitochondrial complex I inhibitor BAY 87-2243 induces a metabolic switch from OXPHOS to glycolysis in melanoma cells. Results of BAY 87-2243-mediated complex I inhibition include a reduction in the total cellular ATP pool and therefore AMPK activation, suppression of ERK1/2 phosphorylation, and the induction of oxidative stress. ROS stress is marked by stabilization of NRF2, phosphorylation of p38 MAPK, and AMPK as well as cell death signaling marked by cleaved PARP.