RAS–RAF–MEK-dependent oxidative cell death involving voltage-dependent anion channels

Nicholas Yagoda, Moritz von Rechenberg, Elma Zaganjor, Andras J. Bauer, Wan Seok Yang, Daniel J. Fridman, Adam J. Wolpaw, Inese Smukste, John M. Peltier, J. Jay Boniface, Richard Smith, Stephen L. Lessnick, Sudhir Sahasrabudhe and Brent R. Stockwell ()
Additional contact information
Nicholas Yagoda: Fairchild Center, 1212 Amsterdam Avenue, MC 2406
Moritz von Rechenberg: Prolexys Pharmaceuticals, 2150 West Dauntless Avenue, Salt Lake City, Utah 84116, USA
Elma Zaganjor: Fairchild Center, 1212 Amsterdam Avenue, MC 2406
Andras J. Bauer: Fairchild Center, 1212 Amsterdam Avenue, MC 2406
Wan Seok Yang: Fairchild Center, 1212 Amsterdam Avenue, MC 2406
Daniel J. Fridman: Fairchild Center, 1212 Amsterdam Avenue, MC 2406
Adam J. Wolpaw: Fairchild Center, 1212 Amsterdam Avenue, MC 2406
Inese Smukste: Fairchild Center, 1212 Amsterdam Avenue, MC 2406
John M. Peltier: Prolexys Pharmaceuticals, 2150 West Dauntless Avenue, Salt Lake City, Utah 84116, USA
J. Jay Boniface: Prolexys Pharmaceuticals, 2150 West Dauntless Avenue, Salt Lake City, Utah 84116, USA
Richard Smith: Center for Children, Huntsman Cancer Institute, 2000 Circle of Hope, Salt Lake City, Utah 84112, USA
Stephen L. Lessnick: Center for Children, Huntsman Cancer Institute, 2000 Circle of Hope, Salt Lake City, Utah 84112, USA
Sudhir Sahasrabudhe: Prolexys Pharmaceuticals, 2150 West Dauntless Avenue, Salt Lake City, Utah 84116, USA
Brent R. Stockwell: Fairchild Center, 1212 Amsterdam Avenue, MC 2406

Nature, 2007, vol. 447, issue 7146, 865-869

Abstract: Mitochondrial target A screen for small molecules that kill tumour cells with mutations in the oncogene HRAS has yielded a compound called erastin. Erastin treatment of cells expressing oncogenic RAS leads to cell death via an oxidative, non-apoptotic mechanism. Erastin acts via mitochondrial voltage-dependent anion channels, a novel target that could lead to new genotype-selective anticancer drugs.

Date: 2007
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DOI: 10.1038/nature05859

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