title: Dithiocarbamate-based coordination compounds as potent proteasome inhibitors in human cancer cells.
abstract: Dithiocarbamates are a class of metal-chelating compounds with various applications in medicine. They have been used for the treatment of bacterial and fungal infections, possible treatment of AIDS, and most recently cancer. Their anti-tumor effects can in part be attributed to their ability to complex tumor cellular copper, leading to binding to and inhibition of the proteasome and in turn initiating tumor cell-specific apoptosis. Current chemotherapeutic agents are highly toxic and therefore their efficacy in the eradication of tumors is greatly limited. As a result many scientists have joined the quest for novel targeted therapies in hopes of reducing toxicity while maximizing potency and proteasome inhibition has become an attractive therapy in this regard. Here we discuss the origins, mechanism, and evolution of dithiocarbamates as potent proteasome inhibitors and therefore anti-cancer agents.
authors.affiliation: Departments of Oncology, Pharmacology and Pathology, and Developmental Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, 4100 John R Street Hudson Webber Cancer Research Center Room 516, Detroit, MI 48201, USA.
authors.forename: Daniela
authors.initials: D
authors.lastname: Buac
authors.forename: Sara
authors.initials: S
authors.lastname: Schmitt
authors.forename: George
authors.initials: G
authors.lastname: Ventro
authors.forename: Fathima Rani
authors.initials: FR
authors.lastname: Kona
authors.forename: Q Ping
authors.initials: QP
authors.lastname: Dou
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use; D056831:Coordination Complexes / Q000737:chemistry / Q000627:therapeutic use; D003300:Copper / Q000737:chemistry; D006046:Gold / Q000737:chemistry; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000378:metabolism*; D061988:Proteasome Inhibitors / Q000737:chemistry* / Q000627:therapeutic use; D013859:Thiocarbamates / Q000737:chemistry*; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015032:Zinc / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D061988:Proteasome Inhibitors; D013859:Thiocarbamates; D006046:Gold; D003300:Copper; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex; D015032:Zinc