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Biotech / Medical : Cell Therapeutics (CTIC) -- Ignore unavailable to you. Want to Upgrade?

To: nigel bates who wrote (194)	3/16/2004 5:11:28 PM
From: tuck	Read Replies (2) \| Respond to of 946

[Role of NADPH oxidase in arsenic-induced reactive oxygen species formation and cytotoxicity in myeloid leukemia cells] >>Published online before print March 15, 2004 Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0306687101 Medical Sciences Role of NADPH oxidase in arsenic-induced reactive oxygen species formation and cytotoxicity in myeloid leukemia cells Wen-Chien Chou , Chunfa Jie , Andrew A. Kenedy ¶, Richard J. Jones \|\|, Michael A. Trush ¶, and Chi V. Dang ¶\|\|** *Program of Human Genetics and Molecular Biology, Department of Medicine, McKusick-Nathans Institute of Genetic Medicine, and \|\|Sidney Kimmel Comprehensive Cancer Center, School of Medicine, ¶Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205 Edited by Owen N. Witte, University of California, Los Angeles, CA, and approved January 21, 2004 (received for review October 16, 2003) Arsenic has played a key medicinal role against a variety of ailments for several millennia, but during the past century its prominence has been displaced by modern therapeutics. Recently, attention has been drawn to arsenic by its dramatic clinical efficacy against acute promyelocytic leukemia. Although toxic reactive oxygen species (ROS) induced in cancer cells exposed to arsenic could mediate cancer cell death, how arsenic induces ROS remains undefined. Through the use of gene expression profiling, interference RNA, and genetically engineered cells, we report here that NADPH oxidase, an enzyme complex required for the normal antibacterial function of white blood cells, is the main target of arsenic-induced ROS production. Because NADPH oxidase enzyme activity can also be stimulated by phorbol myristate acetate, a synergism between arsenic and the clinically used phorbol myristate acetate analog, bryostatin 1, through enhanced ROS production can be expected. We show that this synergism exists, and that the use of very low doses of both arsenic and bryostatin 1 can effectively kill leukemic cells. Our findings pinpoint the arsenic target of ROS production and provide a conceptual basis for an anticancer regimen.<< Relevant, I hope. Cheers, Tuck