Antitumor and antiinflammatory effects of tetrathiotungstate in comparison with tetrathiomolybdate.
Tetrathiomolybdate (TM) is an anticopper drug under development for treating Wilson's disease. Its mechanism of action involves forming a tight tripartite complex in the blood with serum albumin and available copper. When available copper levels are lowered in animals with TM, strong antiangiogenic and antitumor effects are observed. Similarly, TM has excellent efficacy in animal models of fibrotic, inflammatory, and autoimmune diseases, and it protects against heart damage from doxorubicin (DXR) and liver damage from acetaminophen, carbon tetrachloride, and concanavalin A. Tetrathiotungstate (TT) also forms a similar tripartite complex in the blood and has similar effects to TM on copper. In this article, whether TT had similar antitumor effects, and similar effects in protecting the heart against DXR toxicity, as TM was evaluated. It was found that the 2 drugs were comparable in their effects when doses were used that lowered copper availability to the same extent.
Hou
Guoqing
G
Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI 48019-0534, USA.
Dick
Robert
R
Zeng
Chunhua
C
Brewer
George J
GJ
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D018827:Carcinoma, Lewis Lung / Q000473:pathology; D002570:Ceruloplasmin / Q000032:analysis; D003300:Copper / Q000037:antagonists & inhibitors; D052279:Creatine Kinase, MB Form / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000506:poisoning; D006331:Heart Diseases / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control; D007249:Inflammation / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008175:Lung Neoplasms / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008982:Molybdenum / Q000008:administration & dosage / Q000494:pharmacology*; D019210:Troponin I / Q000097:blood; D017973:Tungsten Compounds / Q000008:administration & dosage / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D015415:Biomarkers; D019210:Troponin I; D017973:Tungsten Compounds; C020863:ammonium tetrathiotungstate; D003300:Copper; D004317:Doxorubicin; D008982:Molybdenum; C020809:tetrathiomolybdate; D007770:L-Lactate Dehydrogenase; D002570:Ceruloplasmin; D052279:Creatine Kinase, MB Form