Xanthine dehydrogenase and its role in cancer chemotherapy.
Xanthine dehydrogenase (EC 1.1.1.204) is a molybdenum iron-sulfur, flavin hydroxylase whose physiological role is ascribed to purine catabolism. Its ready conversion to its oxidase counterpart, xanthine oxidase (EC 1.1.3.22), under normal isolation conditions has complicated studies of this enzyme in the past. Many studies in the past have looked at the role of xanthine oxidase in the metabolism of chemotherapeutic agents requiring bioreductive activation for their antineoplastic activities. This paper reviews some of xanthine dehydrogenase's biological and physiological parameters as well as recent studies into the xanthine dehydrogenase-induced activation of bioreductive agents. Studies are also presented that point out this enzyme's potential role in mitomycin C-induced cytotoxicity to EMT6 cells under aerobic and hypoxic conditions. The potential importance of xanthine dehydrogenase as an enzyme targeted in chemotherapeutic regimens is discussed.
Pritsos
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CA
Department of Nutrition, University of Nevada, Reno 89557, USA.
Gustafson
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D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D001711:Biotransformation; D006801:Humans; D016685:Mitomycin / Q000493:pharmacokinetics; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D010084:Oxidation-Reduction; D014968:Xanthine Dehydrogenase / Q000502:physiology*
D000970:Antineoplastic Agents; D016685:Mitomycin; D014968:Xanthine Dehydrogenase; D016660:NAD(P)H Dehydrogenase (Quinone)