A redox-inactive thioredoxin reduces growth and enhances apoptosis in WEHI7.2 cells.
Cancer cell lines transfected with thioredoxin show increased anchorage-independent growth and decreased sensitivity to induction of apoptosis by a number of anticancer drugs. The present studies were undertaken to evaluate further the role of thioredoxin in cell growth and drug-induced apoptosis. A redox-inactive mutant thioredoxin was stably transfected into WEHI7.2 mouse lymphocytic leukemia cells and two clones were examined for growth characteristics and the induction of apoptosis by dexamethasone, etoposide, doxorubicin, and staurosporine. These clones each exhibited a 71% increase in doubling time in solution and a 20 and 75% reduction in colony formation in soft agarose. The transfected cells also showed increased susceptibility to apoptosis induced by dexamethasone, etoposide, doxorubicin, and staurosporine compared with controls. The results of this study suggest that thioredoxin can regulate the growth rate of cells and that thioredoxin is a critical component in the pathway leading to drug-induced apoptosis in WEHI7.2 cells.
Freemerman
A J
AJ
Arizona Cancer Center, University of Arizona, 1515 North Campbell Avenue, Tucson, Arizona 85724-5024, USA.
Powis
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G
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018076:DNA, Complementary / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D005799:Genes, Dominant; D006801:Humans; D051379:Mice; D009154:Mutation; D010084:Oxidation-Reduction; D019311:Staurosporine / Q000494:pharmacology; D013879:Thioredoxins / Q000235:genetics* / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D000972:Antineoplastic Agents, Phytogenic; D018076:DNA, Complementary; D004791:Enzyme Inhibitors; D013879:Thioredoxins; D005047:Etoposide; D003907:Dexamethasone; D004317:Doxorubicin; D019311:Staurosporine