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Pathway Description
Epirubicin Action Pathway
Homo sapiens
Category:
Metabolite Pathway
Sub-Category:
Drug Action
Created: 2023-09-01
Last Updated: 2023-11-27
Epirubicin is an anthracycline topoisomerase II inhibitor used an adjuvant to treating axillary node metastases in patients who have undergone surgical resection of primary breast cancer.
It inhibits cellular reproduction by interfering with DNA replication. Also, it may contribute to the induction of apoptosis by increasing the oxidative stress of the cell through the generation of reactive oxygen species and free radicals. Epirubicin carries significant toxicities including cytopenias, hepatotoxicity, and extravasation reactions. Like other anthracyclines, daunorubicin exhibits cardiotoxicity that is in proportion to the cumulative dose of the drug. Epirubicin acts by forming many complexes with DNA, by intercalation between base pairs, and it inhibits topoisomerase II (2-alpha and 2-beta) activity by stabilizing the DNA-topoisomerase II complex, preventing the religation portion of the ligation-religation reaction that topoisomerase II normally catalyzes. By doing this, the cell will not be able to continue its replication and will die through apoptosis.
References
Epirubicin Pathway References
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
Ganzina F: 4'-epi-doxorubicin, a new analogue of doxorubicin: a preliminary overview of preclinical and clinical data. Cancer Treat Rev. 1983 Mar;10(1):1-22. doi: 10.1016/s0305-7372(83)80029-2.
Pubmed: 6342772
Williams LD, Frederick CA, Ughetto G, Rich A: Ternary interactions of spermine with DNA: 4'-epiadriamycin and other DNA: anthracycline complexes. Nucleic Acids Res. 1990 Sep 25;18(18):5533-41. doi: 10.1093/nar/18.18.5533.
Pubmed: 2216725
Podell ER, Harrington DJ, Taatjes DJ, Koch TH: Crystal structure of epidoxorubicin-formaldehyde virtual crosslink of DNA and evidence for its formation in human breast-cancer cells. Acta Crystallogr D Biol Crystallogr. 1999 Sep;55(Pt 9):1516-23. doi: 10.1107/s0907444999008161.
Pubmed: 10489446
Petit T, Wilt M, Velten M, Millon R, Rodier JF, Borel C, Mors R, Haegele P, Eber M, Ghnassia JP: Comparative value of tumour grade, hormonal receptors, Ki-67, HER-2 and topoisomerase II alpha status as predictive markers in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy. Eur J Cancer. 2004 Jan;40(2):205-11. doi: 10.1016/s0959-8049(03)00675-0.
Pubmed: 14728934
Knoop AS, Knudsen H, Balslev E, Rasmussen BB, Overgaard J, Nielsen KV, Schonau A, Gunnarsdottir K, Olsen KE, Mouridsen H, Ejlertsen B: retrospective analysis of topoisomerase IIa amplifications and deletions as predictive markers in primary breast cancer patients randomly assigned to cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide, epirubicin, and fluorouracil: Danish Breast Cancer Cooperative Group. J Clin Oncol. 2005 Oct 20;23(30):7483-90. doi: 10.1200/JCO.2005.11.007.
Pubmed: 16234514
Liang CH, Shiu LY, Chang LC, Sheu HM, Kuo KW: Solamargine upregulation of Fas, downregulation of HER2, and enhancement of cytotoxicity using epirubicin in NSCLC cells. Mol Nutr Food Res. 2007 Aug;51(8):999-1005. doi: 10.1002/mnfr.200700044.
Pubmed: 17639997
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
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.
Pubmed: 11278867
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.
Pubmed: 15208328
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.
Pubmed: 17050692
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