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Pathway Description
Mitoxantrone Action Pathway
Homo sapiens
Category:
Metabolite Pathway
Sub-Category:
Drug Action
Created: 2023-05-25
Last Updated: 2023-10-25
Mitoxantrone is an anthracenedione-derived chemotherapeutic agent used for the treatment of secondary (chronic) progressive, progressive relapsing, or worsening relapsing-remitting multiple sclerosis. Mitoxantrone binds to DNA, by doing this it intercalates into the acid nucleic chain through hydrogen bonding. This binding ends up causing crosslinks and strand breaks. Mitoxantrone can also interferes with ribonucleic acid (RNA) and is a potent inhibitor of topoisomerase II, the enzyme responsible for uncoiling and repairing damaged DNA. This drug has a cytocidal effect on proliferating cells and nonproliferation cells, this suggests that it is not a cell cycle-specific drug. Mitoxantrone is administered in an intravenous injection.
References
Mitoxantrone Pathway References
Hajihassan Z, Rabbani-Chadegani A: Studies on the binding affinity of anticancer drug mitoxantrone to chromatin, DNA and histone proteins. J Biomed Sci. 2009 Mar 11;16(1):31. doi: 10.1186/1423-0127-16-31.
Pubmed: 19284573
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. doi: 10.1093/nar/30.1.412.
Pubmed: 11752352
Satherley K, de Souza L, Neale MH, Alexander RA, Myatt N, Foss AJ, Hungerford JL, Hickson ID, Cree IA: Relationship between expression of topoisomerase II isoforms and chemosensitivity in choroidal melanoma. J Pathol. 2000 Oct;192(2):174-81. doi: 10.1002/1096-9896(2000)9999:9999<::AID-PATH677>3.0.CO;2-H.
Pubmed: 11004693
Ko MW, Tamhankar MA, Volpe NJ, Porter D, McGrath C, Galetta SL: Acute promyelocytic leukemic involvement of the optic nerves following mitoxantrone treatment for multiple sclerosis. J Neurol Sci. 2008 Oct 15;273(1-2):144-7. doi: 10.1016/j.jns.2008.06.028. Epub 2008 Aug 6.
Pubmed: 18687447
Mazerski J, Martelli S, Borowski E: The geometry of intercalation complex of antitumor mitoxantrone and ametantrone with DNA: molecular dynamics simulations. Acta Biochim Pol. 1998;45(1):1-11.
Pubmed: 9701490
Fox EJ: Management of worsening multiple sclerosis with mitoxantrone: a review. Clin Ther. 2006 Apr;28(4):461-74. doi: 10.1016/j.clinthera.2006.04.013.
Pubmed: 16750460
Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M: DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. doi: 10.1093/nar/gkx1037.
Pubmed: 29126136
Evison BJ, Sleebs BE, Watson KG, Phillips DR, Cutts SM: Mitoxantrone, More than Just Another Topoisomerase II Poison. Med Res Rev. 2016 Mar;36(2):248-99. doi: 10.1002/med.21364. Epub 2015 Aug 19.
Pubmed: 26286294
Tsai-Pflugfelder M, Liu LF, Liu AA, Tewey KM, Whang-Peng J, Knutsen T, Huebner K, Croce CM, Wang JC: Cloning and sequencing of cDNA encoding human DNA topoisomerase II and localization of the gene to chromosome region 17q21-22. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7177-81. doi: 10.1073/pnas.85.19.7177.
Pubmed: 2845399
Wasserman RA, Austin CA, Fisher LM, Wang JC: Use of yeast in the study of anticancer drugs targeting DNA topoisomerases: expression of a functional recombinant human DNA topoisomerase II alpha in yeast. Cancer Res. 1993 Aug 1;53(15):3591-6.
Pubmed: 8393377
Lang AJ, Mirski SE, Cummings HJ, Yu Q, Gerlach JH, Cole SP: Structural organization of the human TOP2A and TOP2B genes. Gene. 1998 Oct 23;221(2):255-66. doi: 10.1016/s0378-1119(98)00468-5.
Pubmed: 9795238
Uchiumi T, Hinoshita E, Haga S, Nakamura T, Tanaka T, Toh S, Furukawa M, Kawabe T, Wada M, Kagotani K, Okumura K, Kohno K, Akiyama S, Kuwano M: Isolation of a novel human canalicular multispecific organic anion transporter, cMOAT2/MRP3, and its expression in cisplatin-resistant cancer cells with decreased ATP-dependent drug transport. Biochem Biophys Res Commun. 1998 Nov 9;252(1):103-10. doi: 10.1006/bbrc.1998.9546.
Pubmed: 9813153
Kiuchi Y, Suzuki H, Hirohashi T, Tyson CA, Sugiyama Y: cDNA cloning and inducible expression of human multidrug resistance associated protein 3 (MRP3). FEBS Lett. 1998 Aug 14;433(1-2):149-52. doi: 10.1016/s0014-5793(98)00899-0.
Pubmed: 9738950
Belinsky MG, Bain LJ, Balsara BB, Testa JR, Kruh GD: Characterization of MOAT-C and MOAT-D, new members of the MRP/cMOAT subfamily of transporter proteins. J Natl Cancer Inst. 1998 Nov 18;90(22):1735-41. doi: 10.1093/jnci/90.22.1735.
Pubmed: 9827529
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