About: Cytochrome b(5) shifts oxidation of the anticancer drug ellipticine by cytochromes P450 1A1 and 1A2 from its detoxication to activation, thereby modulating its pharmacological efficacy

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About: Cytochrome b(5) shifts oxidation of the anticancer drug ellipticine by cytochromes P450 1A1 and 1A2 from its detoxication to activation, thereby modulating its pharmacological efficacy Goto Sponge NotDistinct Permalink

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rdf:type	skos:Concept http://linked.opendata.cz/ontology/domain/vavai/Vysledek
rdfs:seeAlso	http://dx.doi.org/10.1016/j.bcp.2011.06.003
Description	Ellipticine is a pro-drug, whose activation is dependent on its oxidation by cytochromes P450 (CYP) and peroxidases. Cytochrome b(5) alters the ratio of ellipticine metabolites formed by isolated reconstituted CYP1A1 and 1A2, favoring formation of 12-hydroxy- and 13-hydroxyellipticine metabolites implicated in ellipticine-DNA adduct formation, at the expense of 9-hydroxy- and 7-hydroxyellipticine that are detoxication products. Cytochrome b(5) enhances the production of 12-hydroxy and 13-hydroxyellipticine. The change in metabolite ratio results in an increased formation of covalent ellipticine-DNA adducts, one of the DNA-damaging mechanisms of ellipticine antitumor action. This finding explains previous apparent discrepancies found with isolated enzymes and in vivo, where CYP1A enzymatic activation correlated with ellipticine-DNA-adduct levels while isolated CYP1A1 or 1A2 in reconstituted systems were much less effective than CYP3A4. Ellipticine is a pro-drug, whose activation is dependent on its oxidation by cytochromes P450 (CYP) and peroxidases. Cytochrome b(5) alters the ratio of ellipticine metabolites formed by isolated reconstituted CYP1A1 and 1A2, favoring formation of 12-hydroxy- and 13-hydroxyellipticine metabolites implicated in ellipticine-DNA adduct formation, at the expense of 9-hydroxy- and 7-hydroxyellipticine that are detoxication products. Cytochrome b(5) enhances the production of 12-hydroxy and 13-hydroxyellipticine. The change in metabolite ratio results in an increased formation of covalent ellipticine-DNA adducts, one of the DNA-damaging mechanisms of ellipticine antitumor action. This finding explains previous apparent discrepancies found with isolated enzymes and in vivo, where CYP1A enzymatic activation correlated with ellipticine-DNA-adduct levels while isolated CYP1A1 or 1A2 in reconstituted systems were much less effective than CYP3A4. (en)
Title	Cytochrome b(5) shifts oxidation of the anticancer drug ellipticine by cytochromes P450 1A1 and 1A2 from its detoxication to activation, thereby modulating its pharmacological efficacy Cytochrome b(5) shifts oxidation of the anticancer drug ellipticine by cytochromes P450 1A1 and 1A2 from its detoxication to activation, thereby modulating its pharmacological efficacy (en)
skos:prefLabel	Cytochrome b(5) shifts oxidation of the anticancer drug ellipticine by cytochromes P450 1A1 and 1A2 from its detoxication to activation, thereby modulating its pharmacological efficacy Cytochrome b(5) shifts oxidation of the anticancer drug ellipticine by cytochromes P450 1A1 and 1A2 from its detoxication to activation, thereby modulating its pharmacological efficacy (en)
skos:notation	RIV/00216208:11310/11:10100256!RIV12-GA0-11310___
http://linked.open...avai/riv/aktivita	P Z
http://linked.open...avai/riv/aktivity	P(1M0505), P(GA203/09/0812), P(GAP301/10/0356), P(GD305/09/H008), Z(MSM0021620808)
http://linked.open...iv/cisloPeriodika	6
http://linked.open...vai/riv/dodaniDat	2012
http://linked.open...aciTvurceVysledku	Moserová, Michaela Kotrbová, Věra Mrázová, Barbora Hodek, Petr Martínek, Václav Hudeček, Jiří Stiborová, Marie
http://linked.open.../riv/druhVysledku	J - Článek v odborném periodiku
http://linked.open...iv/duvernostUdaju	S - Úplné a pravdivé údaje nepodléhající ochraně podle zvláštních právních předpisů
http://linked.open...titaPredkladatele	Univerzita Karlova v Praze / Přírodovědecká fakulta
http://linked.open...dnocenehoVysledku	192625
http://linked.open...ai/riv/idVysledku	RIV/00216208:11310/11:10100256
http://linked.open...riv/jazykVysledku	eng - angličtina
http://linked.open.../riv/klicovaSlova	Activation; Modulation; Ellipticine; Cytochrome b5; CYP1A1/2 (en)
http://linked.open.../riv/klicoveSlovo	Activation CYP1A1/2 Cytochrome b5 Ellipticine Modulation
http://linked.open...odStatuVydavatele	NL - Nizozemsko
http://linked.open...ontrolniKodProRIV	[0C47E59C0A40]
http://linked.open...i/riv/nazevZdroje	Biochemical Pharmacology
http://linked.open...in/vavai/riv/obor	CE
http://linked.open...ichTvurcuVysledku	7 (xsd:int)
http://linked.open...cetTvurcuVysledku	8 (xsd:int)
http://linked.open...vavai/riv/projekt	Center of targeted therapeutic drugs Mechanism of modulation of cytochrome P450 1A1/2 mediated oxidation of drugs and carcinogens by cytochrome b5; experimental and computational approach Study of contribution of different DNA-damaging mechanisms to toxicity of cytostatics to human chemosensitive and chemoresistant neuroblastomas Preparation, biotransformation, and optimalization of compounds with antitumor and antimicrobial effects
http://linked.open...UplatneniVysledku	2011
http://linked.open...v/svazekPeriodika	82
http://linked.open...iv/tvurceVysledku	Frei, Eva Hodek, Petr Hudeček, Jiří Martínek, Václav Stiborová, Marie Kotrbová, Věra Moserová, Michaela Mrázová, Barbora
http://linked.open...ain/vavai/riv/wos	000294103900009
http://linked.open...n/vavai/riv/zamer	Molekulárně biologické, genetické a epigenetické aspekty vzniku a rozvoje modelových tumorů dospělého věku. Význam pro epidemiologii, časnou diagnostiku a léčbu
issn	0006-2952
number of pages	12 (xsd:int)
http://bibframe.org/vocab/doi	10.1016/j.bcp.2011.06.003
http://localhost/t...ganizacniJednotka	11310

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