Journal
FEBS LETTERS
Volume 581, Issue 1, Pages 118-124Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.febslet.2006.12.016
Keywords
arsenic trioxide; apoptosis; c-Jun NH2-terminal kinase; Rho; ROCK
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The apoptotic signals activated by As(2)O(3) in the chronic myelogenous leukemia (CML) cell lines K562 and KCL22 were investigated. As(2)O(3) was found to induce apoptosis in these cells via the intrinsic pathway. As(2)O(3) also induced a sustained c-Jun NH2-terminal kinase (JNK) activation which preceded and was necessary for caspase-9 activation. We established that Rho and its effector, the kinase ROCK, are activated by As(2)O(3). Inhibition of either Rho or ROCK prevented JNK activation and protected against apoptosis. Thus, in CML cells, apoptosis induced by As(2)O(3) is mediated, at least in part, via a Rho-ROCK-JNK axis. These findings define a novel signaling pathway for As(2)O(3)-induced apoptosis. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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