PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 29104319-0 2017 Cytochrome b5 plays a dual role in the reaction cycle of cytochrome P450 3A4 during oxidation of the anticancer drug ellipticine. ellipticine 117-128 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 57-76 29104319-1 2017 Abstract: Ellipticine is an anticancer agent that forms covalent DNA adducts after enzymatic activation by cytochrome P450 (CYP) enzymes, mainly by CYP3A4. ellipticine 10-21 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 148-154 29104319-5 2017 Using HPLC analysis we detected up to five ellipticine metabolites, which were formed by human hepatic microsomes and human CYP3A4 in the presence of NADPH or NADH. ellipticine 43-54 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 124-130 29104319-8 2017 Using the 32P-postlabeling method two ellipticine-derived DNA adducts were generated by microsomes and the CYP3A4-Supersome system, both in the presence of NADPH and NADH. ellipticine 38-49 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 107-113 29104319-10 2017 In the presence of NADPH or NADH, cytochrome b5 stimulated the CYP3A4-mediated oxidation of ellipticine, but the stimulation effect differed for individual ellipticine metabolites. ellipticine 92-103 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 63-69 29104319-10 2017 In the presence of NADPH or NADH, cytochrome b5 stimulated the CYP3A4-mediated oxidation of ellipticine, but the stimulation effect differed for individual ellipticine metabolites. ellipticine 156-167 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 63-69 29104319-12 2017 The results demonstrate that cytochrome b5 plays a dual role in the CYP3A4-catalyzed oxidation of ellipticine: (1) cytochrome b5 mediates CYP3A4 catalytic activities by donating the first and second electron to this enzyme in its catalytic cycle, indicating that NADH:cytochrome b5 reductase can substitute NADPH-dependent POR in this enzymatic reaction and (2) cytochrome b5 can act as an allosteric modifier of the CYP3A4 oxygenase. ellipticine 98-109 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 68-74 29104319-12 2017 The results demonstrate that cytochrome b5 plays a dual role in the CYP3A4-catalyzed oxidation of ellipticine: (1) cytochrome b5 mediates CYP3A4 catalytic activities by donating the first and second electron to this enzyme in its catalytic cycle, indicating that NADH:cytochrome b5 reductase can substitute NADPH-dependent POR in this enzymatic reaction and (2) cytochrome b5 can act as an allosteric modifier of the CYP3A4 oxygenase. ellipticine 98-109 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 138-144 29104319-12 2017 The results demonstrate that cytochrome b5 plays a dual role in the CYP3A4-catalyzed oxidation of ellipticine: (1) cytochrome b5 mediates CYP3A4 catalytic activities by donating the first and second electron to this enzyme in its catalytic cycle, indicating that NADH:cytochrome b5 reductase can substitute NADPH-dependent POR in this enzymatic reaction and (2) cytochrome b5 can act as an allosteric modifier of the CYP3A4 oxygenase. ellipticine 98-109 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 138-144 28263536-0 2016 Effectiveness of human cytochrome P450 3A4 present in liposomal and microsomal nanoparticles in formation of covalent DNA adducts by ellipticine. ellipticine 133-144 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 23-42 28263536-6 2016 However, since its anticancer efficiency depends on the CYP3A4-mediated metabolism in cancer cells, the aim of our research is to develop nanoparticles containing this enzyme that can be transported to tumor cells, thereby potentiating ellipticine cytotoxicity. ellipticine 236-247 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 56-62 28263536-7 2016 METHODS: The CYP3A4 enzyme encapsulated into two nanoparticle forms, liposomes and microsomes, was tested to activate ellipticine to its reactive species forming covalent DNA adducts. ellipticine 118-129 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 13-19 28263536-9 2016 RESULTS: The CYP3A4 enzyme both in the liposome and microsome nanoparticle forms was efficient to activate ellipticine to species forming DNA adducts. ellipticine 107-118 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 13-19 28263536-10 2016 Two DNA adducts, which are formed from ellipticine metabolites 12-hydroxy- and 13-hydroxyellipticine generated by its oxidation by CYP3A4, were formed by both CYP3A4 nanoparticle systems. ellipticine 39-50 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 131-137 28263536-10 2016 Two DNA adducts, which are formed from ellipticine metabolites 12-hydroxy- and 13-hydroxyellipticine generated by its oxidation by CYP3A4, were formed by both CYP3A4 nanoparticle systems. ellipticine 39-50 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 159-165 28263536-11 2016 A higher effectiveness of CYP3A4 in microsomal than in liposomal nanoparticles to form ellipticine-DNA adducts was found. ellipticine 87-98 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 26-32 28263536-12 2016 CONCLUSION: Further testing in a suitable cancer cell model is encouraged to investigate whether the DNA-damaging effects of ellipticine after its activation by CYP3A4 nanoparticle forms are appropriate for active targeting of this enzyme to specific cancer cells. ellipticine 125-136 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 161-167 22917556-4 2012 13-Hydroxyellipticine, the metabolite forming the major ellipticine-DNA adduct, was generated mainly by CYP3A4 and 1A1, followed by CYP2D6>2C19>1B1>1A2>2E1 and >2C9. ellipticine 10-21 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 104-118 22917556-9 2012 CYP3A4 and 1A1 in the presence of cytochrome b(5) are mainly responsible for bioactivation of ellipticine to DNA adduct 1 (formed by ellipticine-13-ylium from 13-hydroxyellipticine), while 12-hydroxyellipticine generated during the CYP2C19-mediated ellipticine oxidation is the predominant metabolite forming ellipticine-12-ylium that generates ellipticine-DNA adduct 2. ellipticine 94-105 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-14 22167207-10 2011 Based on these studies, we attribute most of the enhancing effects of VPA and TSA on ellipticine cytotoxicity to enhanced ellipticine-DNA adduct formation caused by an increase in levels of cytochrome b5, CYP3A4 and CYP1A1 in neuroblastoma cells. ellipticine 85-96 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 205-211 15548707-7 2004 Using recombinant human enzymes, oxidation of ellipticine to 9-hydroxyellipticine and 7-hydroxyellipticine by CYP1A1/2 and to 13-hydroxyellipticine and N(2)-oxide by CYP3A4 was corroborated. ellipticine 46-57 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 166-172 15548707-8 2004 Homologue modeling and docking of ellipticine to the CYP3A4 active center was used to explain the predominance of ellipticine oxidation by CYP3A4 to 13-hydroxyellipticine and N(2)-oxide. ellipticine 34-45 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 53-59 15548707-8 2004 Homologue modeling and docking of ellipticine to the CYP3A4 active center was used to explain the predominance of ellipticine oxidation by CYP3A4 to 13-hydroxyellipticine and N(2)-oxide. ellipticine 34-45 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 139-145 15548707-8 2004 Homologue modeling and docking of ellipticine to the CYP3A4 active center was used to explain the predominance of ellipticine oxidation by CYP3A4 to 13-hydroxyellipticine and N(2)-oxide. ellipticine 114-125 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 53-59 15548707-8 2004 Homologue modeling and docking of ellipticine to the CYP3A4 active center was used to explain the predominance of ellipticine oxidation by CYP3A4 to 13-hydroxyellipticine and N(2)-oxide. ellipticine 114-125 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 139-145 22917556-9 2012 CYP3A4 and 1A1 in the presence of cytochrome b(5) are mainly responsible for bioactivation of ellipticine to DNA adduct 1 (formed by ellipticine-13-ylium from 13-hydroxyellipticine), while 12-hydroxyellipticine generated during the CYP2C19-mediated ellipticine oxidation is the predominant metabolite forming ellipticine-12-ylium that generates ellipticine-DNA adduct 2. ellipticine 133-144 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-14 22917556-9 2012 CYP3A4 and 1A1 in the presence of cytochrome b(5) are mainly responsible for bioactivation of ellipticine to DNA adduct 1 (formed by ellipticine-13-ylium from 13-hydroxyellipticine), while 12-hydroxyellipticine generated during the CYP2C19-mediated ellipticine oxidation is the predominant metabolite forming ellipticine-12-ylium that generates ellipticine-DNA adduct 2. ellipticine 133-144 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-14 22917556-12 2012 In liver CYP3A4 is the predominant ellipticine activating CYP species, which is expected to result in efficient metabolism after oral ingestion of ellipticine in humans. ellipticine 35-46 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 9-15 22917556-12 2012 In liver CYP3A4 is the predominant ellipticine activating CYP species, which is expected to result in efficient metabolism after oral ingestion of ellipticine in humans. ellipticine 147-158 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 9-15 12123750-3 2002 We examined a panel of genetically engineered V79 cell lines including the parental line V79MZ and recombinant cells expressing the human CYP enzymes CYP1A1, CYP1A2 or CYP3A4 for their ability to activate ellipticine. ellipticine 205-216 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 168-174