emoresistant cells independently of p53 status. These inhibitors killed 98% of ex vivo primary chronic B-lymphocytic leukemia tumor cells while sparing healthy B cells. In orthotopic mouse models of melanoma and pancreatic ductal adenocarcinoma, the compounds reduced tumor size by more than 90% and 60%, respectively, while sparing immune and cardiac functions. Our work provides direct evidence that specific pharmacological targeting of a mitochondrial potassium channel can lead to ROS-mediated selective apoptosis of cancer cells in vivo, without causing significant side effects.
Direct Pharmacological Targeting of a Mitochondrial Ion Channel Selectively Kills Tumor Cells In Vivo
LEANZA, LUIGI;ROMIO, MATTEO;AZZOLINI, MICHELE;TRENTIN, LIVIO;MANAGO', ANTONELLA;VENTURINI, ELISA;MATTAREI, ANDREA;CARRARETTO, LUCA;URBANI, ANDREA;BIASUTTO, LUCIA;MARTINI, VERONICA;SEVERIN, FILIPPO;PERUZZO, ROBERTA;TRIMARCO, VALENTINA;VISENTIN, ANDREA;SEMENZATO, GIANPIETRO CARLO;ZORATTI, MARIO;PARADISI, CRISTINA
;SZABO', ILDIKO'
2017
Abstract
emoresistant cells independently of p53 status. These inhibitors killed 98% of ex vivo primary chronic B-lymphocytic leukemia tumor cells while sparing healthy B cells. In orthotopic mouse models of melanoma and pancreatic ductal adenocarcinoma, the compounds reduced tumor size by more than 90% and 60%, respectively, while sparing immune and cardiac functions. Our work provides direct evidence that specific pharmacological targeting of a mitochondrial potassium channel can lead to ROS-mediated selective apoptosis of cancer cells in vivo, without causing significant side effects.
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