Co-Treatment With Copper Compounds Dramatically Decreases Toxicities Observed With Cisplatin Cancer Therapy And The Anticancer Efficacy Of Some Copper Chelates Supports The Conclusion That Copper Chelate Therapy May Be Markedly More Effective And Less Toxic Than Cisplatin Therapy

• Published in: Current medicinal chemistry Vol. 14; no. 14; pp. 1499 - 1503
• Main Authors: SORENSON, John R. J, WANGILA, Grant W
• Format: Journal Article
• Language: English
• Published: Schiphol Bentham Science Publishers Ltd 01.06.2007; Bentham Science
• Subjects: Ammonia; Ammonium; Animals; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Apoptosis - drug effects; Biological and medical sciences; Bone marrow; Bones, joints and connective tissue. Antiinflammatory agents; Chelates; Chelating Agents - adverse effects; Chelating Agents - chemistry; Chelating Agents - therapeutic use; Cisplatin - administration & dosage; Cisplatin - adverse effects; Cisplatin - chemistry; Copper - chemistry; Copper - therapeutic use; Copper sulfate; General aspects; Humans; Medical sciences; Molybdenum - therapeutic use; Neoplasms - drug therapy; Organometallic Compounds - adverse effects; Organometallic Compounds - chemistry; Organometallic Compounds - therapeutic use; Pharmacology. Drug treatments; Side effects; Sulfates; Antineoplastic agent; Steroid; Divalent metal Complexes; Transition element complexes; Toxicity; redifferentiation; Superoxide dismutase; anticancer; Copper II Complexes; anti-inflammatory; Mechanism of action; Chemical synthesis; Platinum II Complexes; Enzyme; Mimetic; Antiinflammatory agent; androstenedione synthesis; ammonium tetrathiomolybdate; Malignant tumor; Cell differentiation; Biological activity; Cisplatin; Alkylating agent; coppertetrathiomolybdate; Treatment; copper chelates; Carboxylate; Chelating agent; Oxidoreductases; Androstenedione; Thiomolybdates
• ISSN: 0929-8673; 1875-533X
• DOI: 10.2174/092986707780831041

Co-Administration of CuII chelates are reported to decrease life threatening Cisplatin [PtII(NH3)2(CL)2]-induced acute degenerative renal, gastrointestinal, thymic, and bone marrow states consistent with serious necrotizing and immunemediated inflammatory disease. Initially it was found that copper sulfate treatment completely prevented lethality as well as gastric and nephrotoxicity without compromising PtII(NH3)2(CL)2 antineoplastic activity, which led to suggestions that prior CuIItreatment be used clinically to prevent serious side effects of PtII(NH3)2(CL)2-treatment. In the course of these studies it was discovered that CuII-treatments alone inhibited neoplastic growth and increased survival of rat and mouse models of cancer. Subsequently it was discovered that a stable non-toxic and non-polar lipophilic chelate, CopperII 2(3,5-diisopropylsalicylate)4, caused redifferentiation of cultured neuroblastoma and mouse muscle-implanted mammary adenocarcinoma without neoplastic cell killing. Another stable non-toxic and non-polar lipophilic chelate, CopperII 2(3,5-ditertiarybutylsalicylate)4, was found to prevent Bax-initiated and caspases-3-activation mediated apoptosis. These remarkable observations are concluded to be due to enzyme-mimetic or modulating reactivities of CuII chelates and/or facilitation of CuII or I-dependent enzyme syntheses required to overcome inflammatory-neoplastic disease states. Further, approaches to treating neoplastic diseases by removal of Cu from tissues with ammonium tetrathiomolybdate in an anticopper approach to therapy are not well founded based upon existing scientific literature.