Phenformin-induced mitochondrial dysfunction sensitizes hepatocellular carcinoma for dual inhibition of mTOR
SR Veiga, X Ge, CA Mercer, MI Hernandez-Alvarez… - Clinical Cancer …, 2018 - AACR
Purpose: Hepatocellular carcinoma (HCC) ranks second in cancer mortality and has limited
therapeutic options. We recently described the synergistic effect of allosteric and ATP-site
competitive inhibitors against the mTOR for the treatment of HCC. However, such inhibitors
induce hyperglycemia and increase mitochondrial efficiency. Here we determined whether
the mitochondrial complex I inhibitor phenformin could reverse both side effects, impose an
energetic stress on cancer cells, and suppress the growth of HCC. Experimental Design …
therapeutic options. We recently described the synergistic effect of allosteric and ATP-site
competitive inhibitors against the mTOR for the treatment of HCC. However, such inhibitors
induce hyperglycemia and increase mitochondrial efficiency. Here we determined whether
the mitochondrial complex I inhibitor phenformin could reverse both side effects, impose an
energetic stress on cancer cells, and suppress the growth of HCC. Experimental Design …
Phenformin-Induced Mitochondrial Dysfunction Sensitizes Hepatocellular Carcinoma for Dual Inhibition of mTOR
SR Pereira Da Veiga, X Ge, CA Mercer… - … Research, 2018, vol …, 2018 - diposit.ub.edu
Purpose: Hepatocellular carcinoma (HCC) ranks second in cancer mortality and has limited
therapeutic options. We recently described the synergistic effect of allosteric and ATP-site
competitive inhibitors against the mTOR for the treatment of HCC. However, such inhibitors
induce hyperglycemia and increase mitochondrial efficiency. Here we determined whether
the mitochondrial complex I inhibitor phenformin could reverse both side effects, impose an
energetic stress on cancer cells, and suppress the growth of HCC. Experimental Design …
therapeutic options. We recently described the synergistic effect of allosteric and ATP-site
competitive inhibitors against the mTOR for the treatment of HCC. However, such inhibitors
induce hyperglycemia and increase mitochondrial efficiency. Here we determined whether
the mitochondrial complex I inhibitor phenformin could reverse both side effects, impose an
energetic stress on cancer cells, and suppress the growth of HCC. Experimental Design …
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