Topoisomerase II Inhibitors in Cancer Treatment
DOI:
https://doi.org/10.37285/ijpsn.2010.3.4.2Abstract
Topoisomerase II constitutes a family of nuclear enzymes essential to all living cells. These enzymes are capable of transferring one DNA double helix through a transient break in another DNA double helix. Type II topoisomerases play important roles in DNA metabolic processes, in which they are involved in DNA replication, transcription, chromosome condensation and de-condensation. Topoisomerase II is also the cellular target for a number of widely used anticancer agents currently in clinical use, such as the anthracyclines (daunorubicin and doxorubicin), the epipodophyllotoxins (etoposide and teniposide), and the aminoacridines. These agents stimulate the topoisomerase II-cleavable complex, which is a transient configuration of topoisomerase II on DNA in which topoisomerase II is covalently attached to DNA. This causes the accumulation of cytotoxic nonreversible DNA double-strand breaks generated by the processing of such complexes by DNA metabolic processes. As of present, the clinical use of catalytic topoisomerase inhibitors as antineoplastic agents is limited to aclarubicin and MST-16. Both of these compounds are preferentially active toward hematological malignancies and show limited activity toward solid tumors. This review explains the role of topoisomerase inhibitors in cancer therapy.
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DNA topoisomerase, Topoisomerase II inhibitors, Epipodophyllotoxins;, Merbarone
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Anderson JE, Kopecky KJ, Willman CL, Head D, O’Donnell MR, Luthardt FW, Outcome after induction chemotherapy for older patients with acute myeloid leukemia is not improved with mitoxantrone and etoposide compared to cytarabine and daunorubicin: a Southwest Oncology Group study, Blood. 100:3869–3876(2002).
Anderson H, Roberge M, Topoisomerase II inhibitors affect entry into mitosis and chromosome condensation in BHK cells, Cell Growth Differ.7: 83-90 (1996).
Alberts DS, Peng YM, Leigh S, Davis TP, Woodward DL, Disposition of mitoxantrone in cancer patients, Cancer Res.45: 1879–1884 (1985).
Boland MP, Fitzgerald KA, O’Neill LA, Topoisomerase II is required for mitoxantrone to signal NFkB activation in HL60 cells, J Biol Chem. 275:25231–25238 (2000).
Bojanowski K, Lelievre S, Markovits J, Couprie J, Jacquemin-Sablon A, Larsen AK, Suramin is an inhibitor of DNA topoisomerase II in vitro and in Chinese hamster fibrosarcoma cells, Proc Natl Acad Sci USA.89: 3025–302 (1992).
Boritzki TJ, Wolfard TS, Besserer JA, Jackson RC, Fry DW, Inhibition of type II topoisomerase by fostriecin, Biochem Pharmacol. 37: 4063–4068 (1988).
Bridewell DJ, Finlay GJ, Baguley BC, Differential actions of aclarubicin and doxorubicin: The role of topoisomerase I, Oncol Res. 9: 535–542 (1997).
Calvo E, Cortes J, Rodriguez J, Sureda, M, Beltran C, Rebollo J, A Fixed higher dose schedule of suramin plus hydrocortisone in patients with hormone refractory prostate carcinoma; a multicenter phase II study, Cancer. 92: 2435–2443 (2001).
Chen AY, Liu LF, DNA topoisomerases: essential enzymes and lethal targets. Annu Rev Pharmacol Toxicol. 34: 191–218 (1994).
Chen M, Beck WT, Teniposide-resistant CEM cells, which express mutant DNA topoisomerase II alpha, when treated with noncomplex- stabilizing inhibitors of the enzyme, display no cross-resistance and reveal aberrant functions of the mutant enzyme, Cancer Res. 53: 5946–5953 (1993).
Chu DT, Hallas R, Clement, JJ, Alder J, McDonald E, Plattner JJ, Synthesis and antitumour activities of quinolone antineoplastic agents, Drugs Exp Clin Res. 18: 275–282 (1992).
Chu DT, Hallas R, Tanaka SK, Alder J, Balli D, Plattner JJ, Synthesis and antitumour activities of tetracyclic quinolone antineoplastic agents, Drugs Exp Clin Res.20: 177–183 (1994).
Ehninger G, Schuler U, Proksch B, Zeller KP, Blanz J, Pharmacokinetics and metabolism of mitoxantrone. A review, Clin Pharmacokinet. 18: 365–380 (1990).
Eisenberger MA, Reyno LM, Suramin, Cancer Treat Rev. 20: 259– 273 (1994).
Ettinger DS, Finkelstein DM, Ritch PS, Lincoln ST, Blum RH, Study of either ifosfamide or teniposide compared to a standard chemotherapy for extensive disease small cell lung cancer: an Eastern Cooperative Oncology Group randomized study, Lung Cancer.37: 311–318 (2002).
Faulds D, Balfour JA, Chrisp P, Langtry HD, Mitoxantrone. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in the chemotherapy of cancer, Drugs. 41: 400–449 (1991).
Ferrer S, Marce B, Bellosillo N, Villamor F, Activation of mitochondiral apoptotic pathway in mantel cell lymphoma: high sensitivity to mitoxantrone in cases with functional DNA-damage response genes, Oncogene. 23: 8941–8949 (2004).
Felix CA, Leukemias related to treatment with DNA topoisomerase II inhibitors, Med Pediatr Oncol. 36: 525–535 (2001).
Filomenko R, Prevolat L, Rebe C, Cortier M, Jeannin JF, Solary E, Caspase 10 involvement in cytotoxic drug-induced apoptosis of tumor cells, Oncogene. 25: 7635–7645 (2006).
Fortune JM, Osheroff N, Topoisomerase II as a target for anticancer drugs: when enzymes stop being nice, Proc Nucleic Acid Res Mol Biol. 64: 221–253 (2000).
Fortune JM, Osheroff N, Merbarone inhibits the catalytic activity of human topoisomerase IIa by blocking DNA cleavage, J Biol Chem.273: 17643–17650 (1998).
Fry DW, Besserer JA, Boritzki TJ, Transport of the antitumor antibiotic CI-920 into L1210 leukemia cells by the reduced folate carrier system, Cancer Res. 44: 3366–3370 (1984).
Gatto B, Leo E, Drugs acting on the beta isoform of human topoisomerase II, Curr Med Chem. 3: 175–185 (2003).
Glover A, Chun HG, Kleinman LM, Cooney DA, Plowman J, Grieshaber CK, Malspeis L,& Leyland-Jones B. Merbarone: an antitumor agent entering clinical trials, Invest New Drugs. 5: 137-143 (1987).
Gieseler F, Bauer E, Nuessler V, Clark M, Valsamas S, Molecular effects of topoisomerase II inhibitors in AML cell lines: Correlation of apoptosis with topoisomerase II activity but not with DNA damage, Leukemia. 13: 1859–1863 (1999).
Gormley NA, Orphanides G, Meyer A, Cullis PM, Maxwell A, The interaction of coumarin antibiotics with fragments of DNA gyrase B protein, Biochemistry.35:5083–5092 (1996).
Grossman SA, Phuphanich S, Lesser G, Rozental J, Grochow LB, Fisher J, New approaches to brain tumor therapy CNS consortium. Toxicity, efficacy, and pharmacology of suramin in adults with recurrent high-grade gliomas, J Clin Oncol. 19: 3260–3266 (2001).
Hande KR, Etoposide : four decades of development of a topoisomerase II inhibitor, Eur J Cancer. 34: 1514–152 (1998).
Hirota H, Gosky D, Berger NA, Chatterjee S, Interference with topoisomerase II alpha potentiates melphalan cytotoxicity, Int J Oncol. 20: 311 –318,(2002).
Jackson RC, Fry DW, Boritzki TJ, Roberts BJ, Hook KE, Leopold WR, The biochemical pharmacology of CI-920, a structurally novel antibiotic with antileukemic activity, Adv Enzyme Regul. 23: 193–215 (1985).
Kallio M, Lahdetie J, Effects of the DNA topoisomerase II inhibitor merbarone in male mouse meiotic divisions in vivo: Cell cycle arrest and induction of aneuploidy, Environ Mol Mutagen.29:16–27 (1997).
Kellner U , Sehested M, Jensen PB, Gieseler F, Rudolph P, Culprit and victim-DNA topoisomerase II, Lancet Oncol. 3: 235–243 (2002).
Knox JJ, Moore MJ, Treatment of hormone refractory prostate cancer, Semin Urol Oncol. 19: 202–211 (2001).
Lambert JM , Fernandez DJ, Topoisomerase II cleavable complex formation within DNA loop domains, Biochem Pharmacol. 60: 101–109 (2000).
Leopold WR, Shillis JL, Mertus AE, Nelson JM, Roberts BJ, Jackson RC, Anticancer activity of the structurally novel antibiotic Cl-920 and its analogues, Cancer Res. 44: 1928– 1932 (1984).
Lesher GY, Froelich EJ, Gruett MD, Bailey JH, Brundage RP, 1,8-Naphthyridine derivatives. A new class of chemotherapeutic agents, J Med Pharm Chem. 91: 1063–1065 (1962).
Lin CF, Chen CL ,Chang WT, Jan MS , Hsu LL, Wu RH , Sequential caspase-2 and caspase-8 activation of mitochondria during ceramide and etoposide induced apoptosis, J Biol Chem. 279: 40755–40761 (2004).
Liu LF DNA topoisomerase poisons as antitumor drugs, Annu Rev Biochem. 58: 351–375 (1989).
Lodhi IJ, Clift RE, Omann GM, Sweeney JF, McMahon KK, Hinshaw DB, Inhibition of mono-ADP-ribosyltransferase activity during the execution phase of apoptosis prevents apoptotic body formation, Arch Biochem Biophys. 387: 66–77 (2001).
Marigny K, Aubin F, Burgot G, Le Gall E, Gandemar V, Particular cutaneous side effects with etoposide-containing courses: is VP-16 or etoposide phosphate responsible?, Cancer Chemother Pharmacol.55: 244–250 (2005).
Mamber SW, Okasinski WG, Pinter CD, Tunac JB, Antimycotic effects of the novel antitumor agents fostriecin (CI-920), PD 113,270 and PD 113,271, J Antibiot (Tokyo). 39: 1467–1472 (1986).
Montecucco A, Biamonti G, Cellular response to etoposide treatment, Cancer Lett. 252: 9–18 (2007).
Muggia FM, Teniposide: overview of its therapeutic potential in adult cancers, Cancer Chemother Pharmacol.34: S127–S133 (1994).
Neuhaus O, Kieseier BC, Hartung HP, Therapeutic role of mitoxantrone in multiple sclerosis, Pharmacol Ther. 109: 198–209 (2006).
Nitiss JL, Pourquier P, Pommier Y, Aclacinomycin A stabilizes topoisomerase I covalent complexes, Cancer Res. 57: 4564–4569 (1997).
Poochikian GK, Stability of anthracycline antitumor agents in four infusion fluids, Am J Hosp Pharm.38: 483–486 (1981).
Pui CH, Epipodophyllotoxin-related acute myeloid, Lancet.338: 1468 (1991).
Qu G, Croghan GM, Conover C, Erlichman C, Reid JM, Burch PA, et al. , A phase I and pharmacologic study of suramin with sequential adriamycin in patients with advanced solid tumors, Proc Am Assoc Cancer Res. 3: 402 (2002).
Rappa G, Lorico A, Sartorelli AC , Reversal of etoposide resistance in non-P-glycoprotein expressing multidrug resistant tumor cell lines by novobiocin , Cancer Res. 53: 5487–5493 (1993).
Relling MV, Pui CH, Sandlund JT, Rivera GK, Hancock ML, Boyett JM, Adverse effect of anticonvulsants on efficacy of chemotherapy for acute lymphoblastic leukaemia, Lancet. 356: 285–290 (2000).
Robertson JD, Enoksson M, Suomela M, Zhivotovsky B, Orrenius S, Caspase 2 acts upstream of mitochondria to promote cytochrome C release during etoposide-induced apoptosis, J Biol Chem. 277: 29803–29809 (2002).
Smith MA, Rubenstein L, Anderson JR, Arthur D, Catalano PJ, Friedlin B, Secondary leukemia or myelodysplastic syndrome after treatment with intravenous epipodophyllotoxins, J Clin Oncol.17: 569–577 (1999).
Sorensen BS, Sinding J, Andersen AH, Alsner J, Jensen PB, Westergaard O, Mode of action of topoisomerase II- targeting agents at a specific DNA sequence. Uncoupling the DNA binding, cleavage and religation events, J Mol Biol. 228: 778– 786 (1996).
Song S, Wientjes MG, Gan Y, Au JL, Fibroblast growth factors: An epigenetic mechanism of broad spectrum resistance to anticancer drugs, Proc Natl Acad Sci USA. 97: 8658–8663 (2000).
Stahelin HF, von Wartburg A, The chemical and biological route from podophyllotoxin glucoside to etoposide: ninth Cain memorial Award lecture, Cancer Res. 51: 5–15 (1991).
Wells RJ, Adams MT, Alonzo TA , Arceci J, Buckley J, Buxton AB, Mitoxantrone and cytarabine induction, high-dose cytarabine, and etoposide intensification for pediatric patients with relapsed or refractory acute myeloid leukemia: Children's Cancer Group Study 2951, J Clin Oncol. 21: 2940–2947 (2003).
Xiao H, Mao Y, Desai SD, Zhou N , Ting CY, Hwang J ,The topoisomerase II beta circular clamp arrests transcription and signals a 26S proteasome pathway, Proc Natl Acad Sci .100: 3239–3244 (2003).
Yang XH, Sladek TL, Liu X, Butler BR, Froelich CJ, Thor AD, Reconstitution of caspase 3 sensitizes MCF-7 breast cancer cells to doxorubicin- and etoposide-induced apoptosis, Cancer Res. 61: 348–354 (2001).
