Biomaterial Database

The role of NAD(P)H oxidoreductase (DT-Diaphorase) in the bioactivation of quinone-containing antitumor agents: a review. 2000

P L Gutierrez

The University of Maryland Greenebaum Cancer Center, University of Maryland Medical School, Baltimore, 21201, USA. pgutierr@umgcc.umaryland.edu

Bioactivation of quinone-containing anticancer agents has been studied extensively within the context of the chemistry and structure of the individual quinones which may result in various mechanisms of bioactivation and activity. In this review we focus on the two electron enzymatic reduction/activation of quinone-containing anticancer agents by DT Diaphorase (DTD). This enzyme has become important in oncopharmacology because its activity varies with tissues and it has been found to be elevated in tumors. Thus, a selective tumor cell kill can exist for agents that are good substrates for this enzyme. In addition, the enzyme can be induced by a variety of agents, a fact that can be used in chemotherapy. That is induction by a nontoxic agent followed by treatment with a good DT-Diaphorase substrate. A wide variety of anticancer drugs are discussed some of which are not good substrates such as Adriamycin, and some of which are excellent substrates. The latter category includes a variety of quinone containing alkylating agents.

UI	MeSH Term	Description	Entries
D007223	Infant	A child between 1 and 23 months of age.	Infants
D010084	Oxidation-Reduction	A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).	Redox,Oxidation Reduction
D011809	Quinones	Hydrocarbon rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.
D004790	Enzyme Induction	An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis.	Induction, Enzyme
D005609	Free Radicals	Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. Free radicals include reactive oxygen and nitrogen species (RONS). They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated.	Free Radical
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000970	Antineoplastic Agents	Substances that inhibit or prevent the proliferation of NEOPLASMS.	Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D014407	Tumor Cells, Cultured	Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.	Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured
D016660	NAD(P)H Dehydrogenase (Quinone)	A flavoprotein that reversibly catalyzes the oxidation of NADH or NADPH by various quinones and oxidation-reduction dyes. The enzyme is inhibited by dicoumarol, capsaicin, and caffeine.	DT Diaphorase,Menadione Reductase,Phylloquinone Reductase,Quinone Reductase,Vitamin K Reductase,Diaphorase, DT,Reductase, Menadione,Reductase, Phylloquinone,Reductase, Quinone,Reductase, Vitamin K