Thioredoxin redox control of cell growth and death and the effects of inhibitors.
Thioredoxin is a redox protein found over-expressed in some human tumors. Thioredoxin is secreted by tumor cells and stimulates cancer cell growth. Redox activity is essential for growth stimulation by thioredoxin. Cells transfected with thioredoxin cDNA show increased tumor growth and decreased apoptosis in vivo and decreased sensitivity to apoptosis induced by a variety of agents both in vitro and in vivo. Cells transfected with a redox-inactive mutant thioredoxin show inhibited tumor growth in vivo. Thus, thioredoxin offers an attractive target for anticancer drug development. A class of disulfide inhibitors of thioredoxin has been identified. These disulfides inhibit cancer cell growth in culture and have antitumor activity against some human tumor xenografts in animals.
Arizona Cancer Center, University of Arizona, Tucson 85724-5024, USA. gpowis@azcc.arizona.edu
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Powis
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Kirkpatrick
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Angulo
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Baker
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D004220:Disulfides / Q000494:pharmacology; D015195:Drug Design; D006133:Growth Substances / Q000502:physiology; D006801:Humans; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D010084:Oxidation-Reduction; D013880:Thioredoxin-Disulfide Reductase / Q000235:genetics / Q000378:metabolism; D013879:Thioredoxins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004220:Disulfides; D006133:Growth Substances; D013879:Thioredoxins; D013880:Thioredoxin-Disulfide Reductase