The value of proteasome inhibition in cancer. Can the old drug, disulfiram, have a bright new future as a novel proteasome inhibitor?
The major approach to the development of anticancer drugs involves searching for new compounds, efficient against malignancies, which are not, as yet, used clinically. This strategy is time-consuming and expensive. Recent studies have disclosed a surprising, but mechanistically consistent, anticancer activity of disulfiram (antabuse), a drug used for about 50 years in the treatment of alcoholism. Disulfiram has been successfully used to suppress hepatic metastases originating from ocular melanoma. The pharmacokinetics of disulfiram and its pharmacological profile in cancer cell lines and in cancer cells obtained from patients is well known. Disulfiram is a readily available and inexpensive substance whose adverse effects are negligible, compared to classical cancerostatics. In addition, the inhibitory potency of disulfiram against the proteasome conforms to current anticancer strategies and represents a new, promising approach to proteasome inhibition.
Cvek
Boris
B
Department of Medical Chemistry and Biochemistry at Palacky University, Hnevotinska 3, Olomouc 77515, Czech Republic. cvekb@seznam.cz
Dvorak
Zdenek
Z
D000427:Alcohol Deterrents / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001897:Boronic Acids / Q000627:therapeutic use; D000069286:Bortezomib; D004221:Disulfiram / Q000494:pharmacology / Q000627:therapeutic use*; D004354:Drug Screening Assays, Antitumor; D005544:Forecasting; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D011719:Pyrazines / Q000627:therapeutic use; D013859:Thiocarbamates / Q000494:pharmacology / Q000627:therapeutic use; D025801:Ubiquitin / Q000378:metabolism
D000427:Alcohol Deterrents; D000970:Antineoplastic Agents; D001897:Boronic Acids; D016328:NF-kappa B; D061988:Proteasome Inhibitors; D011719:Pyrazines; D013859:Thiocarbamates; D025801:Ubiquitin; D000069286:Bortezomib; D046988:Proteasome Endopeptidase Complex; D004221:Disulfiram