
Loading Pathway...
Doxorubicin Metabolism Pathway
Doxorubicin Pathway References
Mordente A, Meucci E, Silvestrini A, Martorana GE, Giardina B: New developments in anthracycline-induced cardiotoxicity. Curr Med Chem. 2009;16(13):1656-72.
Minotti G: Reactions of adriamycin with microsomal iron and lipids. Free Radic Res Commun. 1989;7(3-6):143-8.
Thornalley PJ, Bannister WH, Bannister JV: Reduction of oxygen by NADH/NADH dehydrogenase in the presence of adriamycin. Free Radic Res Commun. 1986;2(3):163-71.
Nohl H, Gille L, Staniek K: The exogenous NADH dehydrogenase of heart mitochondria is the key enzyme responsible for selective cardiotoxicity of anthracyclines. Z Naturforsch C. 1998 Mar-Apr;53(3-4):279-85.
Vasquez-Vivar J, Martasek P, Hogg N, Masters BS, Pritchard KA Jr, Kalyanaraman B: Endothelial nitric oxide synthase-dependent superoxide generation from adriamycin. Biochemistry. 1997 Sep 23;36(38):11293-7. doi: 10.1021/bi971475e.
Fogli S, Nieri P, Breschi MC: The role of nitric oxide in anthracycline toxicity and prospects for pharmacologic prevention of cardiac damage. FASEB J. 2004 Apr;18(6):664-75. doi: 10.1096/fj.03-0724rev.
Pawlowska J, Tarasiuk J, Wolf CR, Paine MJ, Borowski E: Differential ability of cytostatics from anthraquinone group to generate free radicals in three enzymatic systems: NADH dehydrogenase, NADPH cytochrome P450 reductase, and xanthine oxidase. Oncol Res. 2003;13(5):245-52.
Gustafson DL, Swanson JD, Pritsos CA: Role of xanthine oxidase in the potentiation of doxorubicin-induced cardiotoxicity by mitomycin C. Cancer Commun. 1991 Sep;3(9):299-304.
Minotti G, Recalcati S, Mordente A, Liberi G, Calafiore AM, Mancuso C, Preziosi P, Cairo G: The secondary alcohol metabolite of doxorubicin irreversibly inactivates aconitase/iron regulatory protein-1 in cytosolic fractions from human myocardium. FASEB J. 1998 May;12(7):541-52.
Miyamoto Y, Koh YH, Park YS, Fujiwara N, Sakiyama H, Misonou Y, Ookawara T, Suzuki K, Honke K, Taniguchi N: Oxidative stress caused by inactivation of glutathione peroxidase and adaptive responses. Biol Chem. 2003 Apr;384(4):567-74. doi: 10.1515/BC.2003.064.
Licata S, Saponiero A, Mordente A, Minotti G: Doxorubicin metabolism and toxicity in human myocardium: role of cytoplasmic deglycosidation and carbonyl reduction. Chem Res Toxicol. 2000 May;13(5):414-20.
Okabe M, Unno M, Harigae H, Kaku M, Okitsu Y, Sasaki T, Mizoi T, Shiiba K, Takanaga H, Terasaki T, Matsuno S, Sasaki I, Ito S, Abe T: Characterization of the organic cation transporter SLC22A16: a doxorubicin importer. Biochem Biophys Res Commun. 2005 Aug 5;333(3):754-62. doi: 10.1016/j.bbrc.2005.05.174.
Eraly SA, Nigam SK: Novel human cDNAs homologous to Drosophila Orct and mammalian carnitine transporters. Biochem Biophys Res Commun. 2002 Oct 11;297(5):1159-66. doi: 10.1016/s0006-291x(02)02343-4.
Gong S, Lu X, Xu Y, Swiderski CF, Jordan CT, Moscow JA: Identification of OCT6 as a novel organic cation transporter preferentially expressed in hematopoietic cells and leukemias. Exp Hematol. 2002 Oct;30(10):1162-9.
Jaiswal AK: Human NAD(P)H:quinone oxidoreductase (NQO1) gene structure and induction by dioxin. Biochemistry. 1991 Nov 5;30(44):10647-53. doi: 10.1021/bi00108a007.
Jaiswal AK, McBride OW, Adesnik M, Nebert DW: Human dioxin-inducible cytosolic NAD(P)H:menadione oxidoreductase. cDNA sequence and localization of gene to chromosome 16. J Biol Chem. 1988 Sep 25;263(27):13572-8.
Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. doi: 10.1038/ng1285. Epub 2003 Dec 21.
Shephard EA, Palmer CN, Segall HJ, Phillips IR: Quantification of cytochrome P450 reductase gene expression in human tissues. Arch Biochem Biophys. 1992 Apr;294(1):168-72. doi: 10.1016/0003-9861(92)90152-m.
Hillier LW, Fulton RS, Fulton LA, Graves TA, Pepin KH, Wagner-McPherson C, Layman D, Maas J, Jaeger S, Walker R, Wylie K, Sekhon M, Becker MC, O'Laughlin MD, Schaller ME, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Cordes M, Du H, Sun H, Edwards J, Bradshaw-Cordum H, Ali J, Andrews S, Isak A, Vanbrunt A, Nguyen C, Du F, Lamar B, Courtney L, Kalicki J, Ozersky P, Bielicki L, Scott K, Holmes A, Harkins R, Harris A, Strong CM, Hou S, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Leonard S, Rohlfing T, Rock SM, Tin-Wollam AM, Abbott A, Minx P, Maupin R, Strowmatt C, Latreille P, Miller N, Johnson D, Murray J, Woessner JP, Wendl MC, Yang SP, Schultz BR, Wallis JW, Spieth J, Bieri TA, Nelson JO, Berkowicz N, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Bedell JA, Mardis ER, Clifton SW, Chissoe SL, Marra MA, Raymond C, Haugen E, Gillett W, Zhou Y, James R, Phelps K, Iadanoto S, Bubb K, Simms E, Levy R, Clendenning J, Kaul R, Kent WJ, Furey TS, Baertsch RA, Brent MR, Keibler E, Flicek P, Bork P, Suyama M, Bailey JA, Portnoy ME, Torrents D, Chinwalla AT, Gish WR, Eddy SR, McPherson JD, Olson MV, Eichler EE, Green ED, Waterston RH, Wilson RK: The DNA sequence of human chromosome 7. Nature. 2003 Jul 10;424(6945):157-64. doi: 10.1038/nature01782.
Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. doi: 10.1101/gr.2596504.
Levartovsky D, Lagziel A, Sperling O, Liberman U, Yaron M, Hosoya T, Ichida K, Peretz H: XDH gene mutation is the underlying cause of classical xanthinuria: a second report. Kidney Int. 2000 Jun;57(6):2215-20. doi: 10.1046/j.1523-1755.2000.00082.x.
Ichida K, Amaya Y, Noda K, Minoshima S, Hosoya T, Sakai O, Shimizu N, Nishino T: Cloning of the cDNA encoding human xanthine dehydrogenase (oxidase): structural analysis of the protein and chromosomal location of the gene. Gene. 1993 Nov 15;133(2):279-84. doi: 10.1016/0378-1119(93)90652-j.
Xu P, Huecksteadt TP, Harrison R, Hoidal JR: Molecular cloning, tissue expression of human xanthine dehydrogenase. Biochem Biophys Res Commun. 1994 Mar 15;199(2):998-1004. doi: 10.1006/bbrc.1994.1328.
Itoda M, Saito Y, Komamura K, Ueno K, Kamakura S, Ozawa S, Sawada J: Twelve novel single nucleotide polymorphisms in ABCB1/MDR1 among Japanese patients with ventricular tachycardia who were administered amiodarone. Drug Metab Pharmacokinet. 2002;17(6):566-71.
Chen CJ, Chin JE, Ueda K, Clark DP, Pastan I, Gottesman MM, Roninson IB: Internal duplication and homology with bacterial transport proteins in the mdr1 (P-glycoprotein) gene from multidrug-resistant human cells. Cell. 1986 Nov 7;47(3):381-9. doi: 10.1016/0092-8674(86)90595-7.
Chen CJ, Clark D, Ueda K, Pastan I, Gottesman MM, Roninson IB: Genomic organization of the human multidrug resistance (MDR1) gene and origin of P-glycoproteins. J Biol Chem. 1990 Jan 5;265(1):506-14.
Ito K, Olsen SL, Qiu W, Deeley RG, Cole SP: Mutation of a single conserved tryptophan in multidrug resistance protein 1 (MRP1/ABCC1) results in loss of drug resistance and selective loss of organic anion transport. J Biol Chem. 2001 May 11;276(19):15616-24. doi: 10.1074/jbc.M011246200. Epub 2001 Feb 21.
Situ D, Haimeur A, Conseil G, Sparks KE, Zhang D, Deeley RG, Cole SP: Mutational analysis of ionizable residues proximal to the cytoplasmic interface of membrane spanning domain 3 of the multidrug resistance protein, MRP1 (ABCC1): glutamate 1204 is important for both the expression and catalytic activity of the transporter. J Biol Chem. 2004 Sep 10;279(37):38871-80. doi: 10.1074/jbc.M403832200. Epub 2004 Jun 18.
Mitra P, Oskeritzian CA, Payne SG, Beaven MA, Milstien S, Spiegel S: Role of ABCC1 in export of sphingosine-1-phosphate from mast cells. Proc Natl Acad Sci U S A. 2006 Oct 31;103(44):16394-9. doi: 10.1073/pnas.0603734103. Epub 2006 Oct 18.
Arlanov R, Porter A, Strand D, Brough R, Karpova D, Kerb R, Wojnowski L, Schwab M, Lang T: Functional characterization of protein variants of the human multidrug transporter ABCC2 by a novel targeted expression system in fibrosarcoma cells. Hum Mutat. 2012 Apr;33(4):750-62. doi: 10.1002/humu.22041. Epub 2012 Feb 28.
Taniguchi K, Wada M, Kohno K, Nakamura T, Kawabe T, Kawakami M, Kagotani K, Okumura K, Akiyama S, Kuwano M: A human canalicular multispecific organic anion transporter (cMOAT) gene is overexpressed in cisplatin-resistant human cancer cell lines with decreased drug accumulation. Cancer Res. 1996 Sep 15;56(18):4124-9.
Buchler M, Konig J, Brom M, Kartenbeck J, Spring H, Horie T, Keppler D: cDNA cloning of the hepatocyte canalicular isoform of the multidrug resistance protein, cMrp, reveals a novel conjugate export pump deficient in hyperbilirubinemic mutant rats. J Biol Chem. 1996 Jun 21;271(25):15091-8. doi: 10.1074/jbc.271.25.15091.
Zhang W, Mojsilovic-Petrovic J, Andrade MF, Zhang H, Ball M, Stanimirovic DB: The expression and functional characterization of ABCG2 in brain endothelial cells and vessels. FASEB J. 2003 Nov;17(14):2085-7. doi: 10.1096/fj.02-1131fje. Epub 2003 Sep 4.
Ozvegy-Laczka C, Koblos G, Sarkadi B, Varadi A: Single amino acid (482) variants of the ABCG2 multidrug transporter: major differences in transport capacity and substrate recognition. Biochim Biophys Acta. 2005 Feb 1;1668(1):53-63. doi: 10.1016/j.bbamem.2004.11.005.
Henriksen U, Gether U, Litman T: Effect of Walker A mutation (K86M) on oligomerization and surface targeting of the multidrug resistance transporter ABCG2. J Cell Sci. 2005 Apr 1;118(Pt 7):1417-26. doi: 10.1242/jcs.01729. Epub 2005 Mar 15.
Jullien-Flores V, Dorseuil O, Romero F, Letourneur F, Saragosti S, Berger R, Tavitian A, Gacon G, Camonis JH: Bridging Ral GTPase to Rho pathways. RLIP76, a Ral effector with CDC42/Rac GTPase-activating protein activity. J Biol Chem. 1995 Sep 22;270(38):22473-7. doi: 10.1074/jbc.270.38.22473.
Awasthi S, Cheng J, Singhal SS, Saini MK, Pandya U, Pikula S, Bandorowicz-Pikula J, Singh SV, Zimniak P, Awasthi YC: Novel function of human RLIP76: ATP-dependent transport of glutathione conjugates and doxorubicin. Biochemistry. 2000 Aug 8;39(31):9327-34. doi: 10.1021/bi992964c.