Ellipticines as DNA-targeted chemotherapeutics

Current Medicinal Chemistry

Volumn 21, Issue 5, 2014, Pages 575-591

  Stiborová, Marie ^a   Frei, Eva ^b  

^a CHARLES UNIVERSITY   (Czech Republic)

^b GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

Author keywords

Anticancer drugs; Apoptosis; DNA damaging drugs; Ellipticines; Mechanisms of ellipticine anticancer action

Indexed keywords

9 HYDROXYELLIPTICINE; CYTOCHROME B5; CYTOCHROME P450; DNA TOPOISOMERASE (ATP HYDROLYSING); ELLIPTICINE; GYRASE INHIBITOR; PEROXIDASE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; SULFOTRANSFERASE;

ANOREXIA; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CANCER CELL; CELL CYCLE ARREST; CHEMOTHERAPY INDUCED NAUSEA AND VOMITING; DNA ADDUCT; DNA DAMAGE; DRUG CYTOTOXICITY; DRUG DETOXIFICATION; DRUG EFFICACY; ENZYME ACTIVITY; ENZYME METABOLISM; ESOPHAGUS DISEASE; ESOPHAGUS MYCOSIS; FATIGUE; GENE TARGETING; HUMAN; HYPERTENSION; KIDNEY FAILURE; MUSCLE CRAMP; TONGUE DISEASE; TONGUE MYCOSIS; XEROSTOMIA;

ANTINEOPLASTIC AGENTS; APOPTOSIS; CYTOCHROME P-450 ENZYME SYSTEM; DNA; DNA ADDUCTS; DNA DAMAGE; DNA TOPOISOMERASES, TYPE II; ELLIPTICINES; HUMANS; NEOPLASMS;

EID: 84893246638     PISSN: 09298673     EISSN: 1875533X     Source Type: Journal    
DOI: 10.2174/09298673113206660272     Document Type: Article

References (174)

1. Goodwin S.; Smith A.F.; Horning E.C. Alkaloids of Ochrosia elliptica Labill, J. Am. Chem. Soc., 1959, 81(8), 1903-1908.
2. Salim A.A.; Garson M.J.; Craik D.J. New indole alkaloids from the roots of Ochrosia acuminata, J. Nat. Prod., 2004, 67(10), 1719-1721.
3. Carroll A.R.; Addepalli R.; Fechner G.; Smith G.; Guymer G.P.; Forster P.I.; Quinn R.J. Alkaloids from the Australian rainforest tree Ochrosia moorei, J. Nat. Prod., 2008, 71(6), 1063-1065.
4. Dalton L.; Demerac S.; Elmes B.; Loder J.; Swan J.; Teitei T. Synthesis of tumour-inhibitory alkaloids ellipticine, 9- methoxyellipticine and related pyrido[4,3/B]carbazoles, Austr. J. Chem., 1967, 20(12), 2715-2717.
5. Paoletti C.; Le Pecq J.B.; Dat-Xuong N.; Juret P.; Garnier H.; Amiel J.L.; Rouesse J. Antitumor activity, pharmacology, and toxicity of ellipticines, ellipticinium, and 9-hydroxy derivatives: preliminary clinical trials of 2-methyl-9-hydroxy ellipticinium (NSC 264-137), Recent Results Cancer Res., 1980, 74, 107-123.
6. Paoletti C.; Auclair C.; Lesca P.; Tocanne J.F.; Malvy C.; Pinto M. Ellipticine, 9-hydroxyellipticine, and 9-hydroxyellipticinum: some biochemical properties of possible pharmacologic significance, Cancer Treat. Rep., 1981, 65(Suppl 3), 107-118.
7. Auclair C. Multimodal action of antitumor agents on DNA: The ellipticine series, Arch. Biochem. Biophys., 1987, 259(1), 1-14.
8. Garbett N.C.; Gravis D.E. Extenting nature's leads: the anticancer agent ellipticine, Curr. Med. Chem. Anti-Cancer Agents, 2004, 4(2), 149-172.
9. Stiborová M.; Sejbal J.; Bořek-Dohalská L.; Aimová D.; Poljaková J.; Forsterová K.; Rupertová M.; Wiesner J.; Hudeček J.; Wiesner M.; Frei E. The anticancer drug ellipticine forms covalent DNA adducts, mediated by human cytochromes P450, through metabolism to 13-hydroxyellipticine and ellipticine N2-oxide, Cancer Res., 2004, 64(22), 8374-8380.
10. Stiborová M.; Rupertová R.; Schmeiser H.H.; Frei E. Molecular mechanism of antineoplastic action of an anticancer drug ellipticine, Biomed. Pap. Med. Fac. Univ. Palacky Olomouc Czech Repub., 2006, 150(1), 13-23.
11. Stiborová M.; Rupertová M.; Frei E. Cytochrome P450- and peroxidase- mediated oxidation of anticancer alkaloid ellipticine dictates its anti-tumor efficiency, Biochim. Biophys. Acta, 2011, 1814(1), 175-185.
12. Kizek R.; Adam V.; Hrabeta J.; Eckschlager T.; Smutny S.; Burda J.V.; Frei E.; Stiborová M. Anthracyclines and ellipticines as DNAdamaging anticancer drugs; Recent advances, Pharmacol. Ther., 2012, 133(10), 26-39.
13. Rouëssé J.G,; Le Chevalier T.; Caille F.; Mondesir J.M.; Sancho-Gamier H.; May-Levin F.; Spielman M.; DeJager R.; Amiel J.L. Phase II study of ellipticinium in advanced breast cancer, Cancer Treat. Rep., 1985, 69(6), 707-708.
14. Mathe G.; Triana K.; Pontiggia P.; Blanquet D.; Hallard M.; Morette C. Data of pre-clinical and early clinical trials of acriflavine and hydroxy-methyl-ellipticine reviewed, enriched by the experience of their use for 18 months to 6 years in combination with other HIV1 virostatic, Biomed. Pharmacother., 1998, 52(9), 391-396.
15. Tian E.; Landowski T.H.; Stephens O.W.; Yaccoby S.; Barlogie B.; Shaughnessy J.D. Jr. Ellipticine derivative NSC 338258 represents a potential new antineoplastic agent for the treatment of multiple myeloma, Mol. Cancer Ther., 2008, 7(3), 500-509.
16. Boyd M.R. Status of the NCI preclinical antitumor drug discovery screen: Implications for selection of new agents for clinical trials, in: V.T. DeVita Jr, S. Hellman, S. Rosenburg (Eds.), Cancer: Principles and Practice of Oncology Updates, Vol. 3, Lippincott, Philadelphia, 1989, pp. 1-12.
17. Boyd M.R. The future of drug development, in: J.E. Niederhuber, (Ed.), Current Therapy in Oncology, B.C. Decker, Philadephia, 1993, pp.11-22.
18. Acton E.M.; Narayanan V.L.; Risbood P.A.; Shoemaker P.H.; Vistica D.T.; Boyd M.R. Anticancer specificity of some ellipticinium salts against human brain tumors in vitro, J. Med. Chem., 1994, 37(14), 2185-2189.
19. Ohashi M.; Sugikawa E.; Nakanishi N. Inhibition of p53 protein phosphorylation by 9-hydroxyellipticine: A possible anticancer mechanism, Jpn. J. Cancer Res., 1995, 86(9), 819-829.
20. Arguello F.; Alexander M.A.; Greene J.F. Jr; Stinson S.F.; Jorden J.L.; Smith E.M.; Kalavar N.T.; Alvord W.G.; Klabansky R.L.; Sausville E.A. Preclinical evaluation of 9-chloro-2- methylellipticinium acetate alone and in combination with conventional anticancer drugs to treatment of human brain tumor xenografts, J. Cancer Res. Clin. Oncol., 1998, 124(1), 19-26.
21. Shi L.M.; Myers T.G.; Fan Y.; O'Connor P.M.; Paull K.D.; Friend S.H.; Weinstein J.N. Mining the National Cancer Institute Anticancer Drug Discovery Database: cluster analysis of ellipticine analogs with p53-inverse and central nervous system-selective patterns of activity, Mol. Pharmacol., 1998, 53(2), 241-251.
22. Stiborová M.; Bieler C.A.; Wiessler M.; Frei E. The anticancer agent ellipticine on activation by cytochrome P450 forms covalent DNA adducts, Biochem. Pharmacol., 2001, 62(12), 675-684.
23. Bořek-Dohalská L.; Frei E.; Stiborová M. DNA adduct formation by the anticancer drug ellipticine and its hydroxy derivatives in human breast adenocarcinoma MCF-7 cells, Collect. Czech. Chem. Commun., 2004, 69(3), 603-615.
24. Moody T.W.; Czerwinski G.; Tarasova N.I.; Moody D.L.; Michejda C.J. The development of VIP-ellipticine conjugates, Regul. Pept., 2004, 123(1-3), 187-192.
25. Kuo P.L.; Hsu Y.L.; Chang C.H.; Lin C.C. The mechanism of ellipticine-induced apoptosis and cell cycle arrest in human breast MCF-7 cancer cells, Cancer Lett., 2005, 223(2), 293-301.
26. Kuo P.L.; Hsu Y.L.; Chang C.H.; Lin C.C. The antiproliferative inhibition of ellipticine in human breast mda-mb-231 cancer cells is through cell cycle arrest and apoptosis induction, Anti-Cancer Drugs, 2005, 16(7), 789-795.
27. Kuo P.L.; Kuo Y.C.; Hsu Y.L.; Cho C.Y.; Lin C.C. Ellipticine induced apoptosis through p53-dependent pathway in human hepatocellular carcinoma HepG2 cells, Life Sci., 2006, 78(22), 2550-2557.
28. Poljaková J.; Frei E.; Gomez J.E.; Aimová D.; Eckschlager T.; Hraběta J.; Stiborová M. DNA adduct formation by the anticancer drug ellipticine in human leukemia HL-60 and CCRF-CEM cells, Cancer Lett., 2007, 252(2), 270-279.
29. Poljaková J.; Eckschlager T.; Hraběta J.; Hřebaková J.; Smutný S.; Frei E.; Martínek V.; Kizek R.; Stiborová M. The mechanism of cytotoxicity and DNA adduct formation by the anticancer drug ellipticine in human neuroblastoma cells, Biochem. Pharmacol., 2009, 77(9), 1466-1479.
30. Poljakova J.; Hrebackova J.; Dvořákova M.; Moserova M.; Eckschlager T.; Hrabeta J.; Göttlicherova M.; Kopekova B.; Frei E.; Kizek R.; Stiborova M. Anticancer agent ellipticine combined with histone deacetylase inhibitors, valproic acid and trichostatin A, is an effective DNA damage strategy in human neuroblastoma, Neuro Endocrinol. Lett., 2011, 32(Suppl 1), 101-116.
31. Poljaková J.; Eckschlager T.; Kizek R.; Frei E.; Stiborová M. Electrochemical determination of enzymes metabolizing ellipticine in thyroid cancer cells - a tool to explain the mechanism of ellipticine toxicity to these cells, Int. J. Electrochem. Sci., 2013, 8(2), 1573-1585.
32. Lu C.; Wang W.; El-Deiry W.S. Non-genotoxic anti-neoplastic effects of ellipticine derivative NSC176327 in p53-deficient human colon carcinoma cells involve stimulation of p73, Cancer Biol. Ther., 2008, 7(12), 2039-2046.
33. Fang K.; Chen S.P.; Lin C.W.; Cheng W.C.; Huang H.T. Ellipticine- induced apoptosis depends on Akt translocation and signaling in lung epithelial cancer cells, Lung Cancer, 2009, 63(2), 227-234.
34. Martinkova E.; Dontenwill M.; Frei E.; Stiborová M.. Cytotoxicity of and DNA adduct formation by ellipticine in human U87MG glioblastoma cancer cells, Neuro Endocrinol. Lett., 2009, 30(Suppl. 1), 60-66.
35. Martinkova E.; Maglott A.; Leger D.Y.; Bonnet D.; Stiborova M.; Takeda K.; Martin S.; Dontenwill M. α5β1 integrin antagonists reduce chemotherapy-induced premature senescence and facilitate apoptosis in human glioblastoma cells, Int. J. Cancer., 2010, 127(5), 1240-1248.
36. Kim J.Y.; Lee S.G.; Chung J.Y.; Kim Y.J.; Park J.E.; Koh H.; Han M.S.; Park Y.C.; Yoo Y.H.; Kim J.M. Ellipticine induces apoptosis in human endometrial cancer cells: the potential involvement of reactive oxygen species and mitogen-activated protein kinases, Toxicology, 2011, 289(2-3), 91-102.
37. Wu Y.; Sadatmousavi P.; Wang R.; Lu S.; Yuan Y.F.; Chen P. Self-assembling peptide-based nanoparticles enhance anticancer effect of ellipticine in vitro and in vivo, Int. J. Nanomedicine, 2012, 7, 3221-3233.
38. Dodion P.; Rozencweig M.; Nicaise C.; Piccart M.; Cumps E.; Crespeigne N.; Kisner D.; Kenis Y. Phase I clinical study of 9- hydroxy-2N-methyl- ellipticinium acetate (NSC-264137) administered on a 5-day i.v. schedule, Eur. J. Cancer Clin. Oncol., 1982, 18(12), 519-522.
39. Juret P.; Tanguy A.; Girard A.; Le Talaer J.Y.; Abbatucci J.S.; Dat-Yuong, Le Pecq J.B.; Paoletti C. Hydroxy 9-methyl 2-ellipticinium acetate (NSC 264-137). Toxicologic study and therapeutic effect in 100 cancers, Nouv. Presse Med., 1979, 8(18), 1495-1498.
40. Juret P.; Couette J.E.; Delozier T.; Le Talaer J.Y. Hydroxy-9- methyl-2-ellipticinium (NSC 264-137) for osseous metastases from breast cancer. A 4 year experience, Bull. Cancer, 1981, 68(3), 224-231.
41. Juret P.; Heron J.F.; Couette J.E.; Delozier T.; Le Talaer J.Y. Hydroxy- 9-methyl-2-ellipticinium for osseous metastases from breast cancer: a 5-year experience, Cancer Treat. Rep., 1982, 66(11), 1909-1916.
42. Rouëssé J.; Spielmann M.; Turpin F.; Le Chevalier T.; Azab M.; Mondésir J.M.; Phase II study of elliptinium acetate salvage treatment of advanced breast cancer, Eur. J. Cancer. 1993, 29A(6), 856-859.
43. Tura S.; Mandelli F.; Mazza P.; Cimino G.; Anselmo A.P.; Amadori S. 2-Methyl-9-hydroxyellipticinium acetate (ellipticinium) in the treatment of lymphomas. Preliminary results of a phase II study, Chemioterapia, 1984, 3(2), 79-82.
44. Amiel J.L.; Rouesse J.; Droz J.P.; Caille P.; Travagli J.P.; Theodore C.; Le Chevalier T.; Ducret J.P.; Bidart M.; Garnier H.S. Treatment of metastatic renal cancer in adults with elliptinium acetate, Presse Med., 1984, 13(25), 1555-1557.
45. Caille P.; Mondesir J.M.; Droz J.P.; Kerbrat P.; Goodman A.; Ducret J.P.; Theodore C.; Spielman M.; Rouesse J.; Amiel, J.L. Phase II trial of elliptinium in advanced renal cell carcinoma, Cancer Treat. Rep., 1985, 69(7), 901-902.
46. Moore M.M.; Brock K.H.; Doerr C.L.; DeMarini D.M. Mutagenesis of L5178Y/TK(+/-)-3.7.2C mouse lymphoma cells by the clastogen ellipticine, Environ. Mutagen., 1987, 9(2), 161-170.
47. DeMarini D.M.; Cros S.; Paoletti C.; Lecointe P.; Hsie A.W. Mutagenicity and cytotoxicity of five antitumor ellipticines in mammalian cells and their structure-activity relationships in Salmonella, Cancer Res., 1983, 43(8), 3544-3552.
48. Sakamoto-Hojo E.T.; Takahashi C.S. Clastogenic action of ellipticine over the cell cycle of human lymphocytes and influence of posttreatments with caffeine and ara-C at G2, Mutat. Res., 1991, 248(1), 195-202.
49. Noviello E.; Aluigi M.G.; Cimoli G.; Rovini E.; Mazzoni A.; Parodi S.; De Sessa F.; Russo P. Sister-chromatid exchanges, chromosomal aberrations and cytotoxicity produced by topoisomerase II-targeted drugs in sensitive (A2780) and resistant (A2780-DX3) human ovarian cancer cells: correlations with the formation of DNA double-strand breaks, Mutat. Res., 1994, 311(1), 21-29.
50. Sugikawa E.; Hosoi T.; Yazaki N.; Gamanuma N.; Nakanishi N.; Ohashi M. Mutant p53 mediated induction of cell cycle arrest and apoptosis at G1 phase by 9-hydroxyellipticine, Anticancer Res., 1999, 19(4B), 3099-3108.
51. Peng Y.; Li C.; Chen L.; Sebti S.; Chen J. Rescue of mutant p53 transcription function by ellipticine, Oncogene, 2003, 22(29), 4478-4487.
52. Mizumoto K.; Sato N.; Kusumoto M.; Niiyama H.; Maehara N.; Nishio S.; Li Z.; Ogawa T.; Tanaka M. Diverse effects of 9- hydroxyellipticine on the chemosensitivity of human pancreatic cancer cells harboring p53 mutations. Cancer Lett., 2000, 149(1-2), 85-94.
53. Fritsche M.; Haessler C.; Brandner G. Induction of nuclear accumulation of the tumor-suppressor protein p53 by DNA-damaging agents. Oncogene, 1993, 8(2), 307-318.
54. Xu G.W.; Mawji I.A.; Macrae C.J.; Koch C.A.; Datti A.; Wrana J.L.; Dennis J.W.; Schimmer A.D. A high-content chemical screen identifies ellipticine as a modulator of p53 nuclear localization, Apoptosis, 2008, 13(3), 413-422.
55. Kovacic P.; Ames J.R.; Lumme P.; Elo H.; Cox O.; Jacson H.; Rivera L.A.; Ramirez L.; Ryan M.D. Change transfer-oxy radical mechanism for anti-cancer agents, Anti-Cancer Drug Design, 1986, 1(3), 197-214.
56. Schwaller M.A.; Allard B.; Lescot E.; Moreau F. Protonophoric activity of ellipticine and isomers across the energy-transducing membrane of mitochondria, J. Biol. Chem., 1995, 270(39), 22709-22713.
57. Hägg M.; Berndtsson M.; Mandic A.; Zhou R.; Shoshan M.C.; Linder S. Induction of endoplasmic reticulum stress by ellipticine plant alkaloids, Mol. Cancer Ther., 2004, 3(4), 489-497.
58. Jin X.; Gossett D.R.; Wang S.; Yang D.; Cao Y.; Chen J.; Guo R.; Reynolds R.K.; Lin J. Inhibition of AKT survival pathway by a small molecule inhibitor in human endometrial cancer cells, Br. J. Cancer, 2004, 91(10), 1808-1812.
59. Tang H.-J.; Jin X.; Wang S.; Yang D.; Cao Y.; Chen J.; Gossett D.R.; Lin J. A small molecule compound inhibits AKT pathway in ovarian cancer cell lines, Gynecol. Oncol., 2006, 100(2), 308-317.
60. Kohn K.W.; Waring M.J.; Glaubiger D.; Friedman C.A. Intercalative binding of ellipticine to DNA, Cancer Res., 1975, 35(1), 71-6.
61. Patel N.; Bergman J.; Gräslund A. 1H-NMR studies of the interaction between a self-complementary deoxyoligonucleotide duplex and indolo[2,3-b]quinoxaline derivatives active against herpes virus, Eur. J. Biochem.. 1991. 197(3), 597-604.
62. Chu Y.; Hsu M.T. Ellipticine increases the superhelical density of intracellular SV40 DNA by intercalation, Nucleic Acids Res.,1992, 20 (15), 4033-4038.
63. Singh M.P.; Hill G.C.; Peoch D.; Rayner B.; Inabach J.L.; Lown J.W. High-field NMR and restrained molecular modeling studies on a DNA heteroduplex containing a modified apurinic abasic site in the form of covalently linked 9-aminoellipticine, Biochemistry, 1994, 33(34), 10271-10285.
64. Monnot M.; Mauffret O.; Simon V.; Lescot E.; Psaume B.; Saucier J.M.; Charra M.; Belehradek J. Jr; Fermandjian S. DNA-drug recognition and effects on topoisomerase II-mediated cytotoxicity. A three-mode binding model for ellipticine derivatives, J. Biol. Chem., 1991, 266(3), 1820-1829.
65. Froelich-Ammon S.J.; Patchan M.W.; Osheroff N.; Thompson R.B. Topoisomerase II binds to ellipticine in the absence or presence of DNA. Characterization of enzyme-drug interactions by fluorescence spectroscopy, J. Biol. Chem., 1995, 270(25), 14998-5004.
66. Stiborová M.; Breuer A.; Aimová D.; Stiborová- Rupertová M.; Wiessler M.; Frei E. DNA adduct formation by the anticancer drug ellipticine in rats determined by 32P-postlabeling, Int. J. Cancer, 2003; 107(6), 885-890.
67. Stiborová M.; Stiborová-Rupertová M.; Bořek-Dohalská L.; Wiessler M.; Frei E. Rat microsomes activating the anticancer drug ellipticine to species covalently binding to deoxyguanosine in DNA are a suitable model mimicking ellipticine bioactivation in humans, Chem. Res. Toxicol., 2003, 16(1), 38-47.
68. Stiborová M.; Poljaková J.; Ryšlavá H.; Dračínský M.; Eckschlager T.; Frei E. Mammalian peroxidases activate anticancer drug ellipticine to intermediates forming deoxyguanosine adducts in DNA identical to those found in vivo and generated from 12- hydroxyellipticine and 13-hydroxyellipticine, Int. J. Cancer, 2007, 120(2), 243-251.
69. Stiborová M.; Rupertová M.; Aimová D.; Ryšlavá H.; Frei E. Formation and persistence of DNA adducts of anticancer drug ellipticine in rats, Toxicology, 2007, 236(1-2), 50-60.
70. Stiborová M.; Indra R.; Moserová M.; Černá V.; Rupertová M.; Martínek V.; Eckschlager T.; Kizek R.; Frei E. Cytochrome b5 increases cytochrome P450 3A4-mediated activation of anticancer drug ellipticine to 13-hydroxyellipticine whose covalent binding to DNA is elevated by sulfotransferases and N,O-acetyltransferases. Chem. Res. Toxicol., 2012, 25(5), 1075-1085.
71. Stiborová M.; Poljakova J.; Martínková E.; Ulrichová J.; Šimánek V.; Dvořák Z.; Frei E. Ellipticine oxidation and DNA adduct formation in human hepatocytes is catalyzed by human cytochromes P450 and enhanced by cytochrome b5, Toxicology, 2012, 302(2-3), 233-241.
72. Kotrbová V.; Aimová D.; Březinová A.; Janouchová K.; Poljaková J.; Hodek P.; Frei E.; Stiborová M. Cytochromes P450 reconstituted with NADPH:P450 reductase mimic the activating and detoxicating metabolism of the anticancer drug ellipticine in microsomes, Neuro Endocrinol. Lett., 2006, 27(Suppl. 2), 18-20.
73. Kotrbová V.; Mrázová B.; Moserová M.; Martínek V.; Hodek P.; Hudeček J.; Frei E.; Stiborová M. Cytochrome b5 shifts oxidation of the anticancer drug ellipticine by cytochromes P450 1A1 and 1A2 from its detoxication to activation, thereby modulating its pharmacological efficacy, Biochem. Pharmacol., 2011, 82(6), 669-680.
74. Dodin G.; Schwaller M.A.; Aubard J.; Paoletti C. Binding of ellipticine base and ellipticinium cation to calf-thymus DNA. A thermodynamic and kinetic study, Eur. J.Biochem., 1988, 176(2), 371-376.
75. Schwaller M.A.; Aubard J.; Auclair C.; Paoletti C.; Dodin G. The G.C base-pair preference of 2-N-methyl 9-hydroxyellipticinium, Eur. J. Biochem., 1989, 181(1), 129-134.
76. Monnot M.; Mauffret O.; Simon V.; Lescot E.; Psaume B.; Saucier J.M.; Belehradek J.; Fermandjian S. A CD study of interactions of ellipticine derivatives with DNA. Relations with the in vitro cytotoxicity, FEBS Lett., 1990, 273(1-2), 71-74.
77. Canals A.; Purciolas M.; Aymami J.; Coll M. The anticancer agent ellipticine unwinds DNA by intercalative binding in an orientation parallel to base pairs, Acta Crystallogr., Sect. D: Biol. Crystallogr., 2005, 61(Pt 7), 1009-1012.
78. Řeha D.; Kabeláč M.; Ryjáček F.; Šponer J.; Šponer J. E.; Elstner M.; Suhai S.; Hobza P. Intercalators. 1. Nature of stacking interactions between intercalators (ethidium, daunomycin, ellipticine, and 4',6-diaminide-2-phenylindole) and DNA base pairs. Ab initio quantum chemical, density functional theory, and empirical potential study, J. Am. Chem. Soc., 2002, 124(13), 3366-3376.
79. Dračínský M.; Castano O. Calculations of interaction energies of ellipticine derivatives with DNA base pairs, Phys. Chem. Chem. Physics , 2004, 6(8), 1799-1805.
80. Holt P.A.; Chaires J.B.; Trent J.O. Molecular docking of intercalators and groove-binders to nucleic acids using Autodock and Surflex, J. Chem. Inf. Model., 2008, 48(8), 1602-1615..
81. Ricci C.G.; Netz P. A. Docking studies on DNA-ligand interactions: building and application of a protocol to identify the binding mode, J. Chem. Inf. Model., 2009, 49(8), 1925-1935.
82. Li S.; Cooper V.R.; Thonhauser T.; Lundqvist B.I.; Langreth D.C. Stacking interactions and DNA intercalation, J. Phys. Chem. B, 2009, 113(32), 11166-11177.
83. Kolář M.; Kubař T.; Hobza P. Sequence-dependent configurational entropy change of DNA upon intercalation, J. Phys. Chem. B, 2010, 114(42), 13446-13454.
84. Huska D.; Adam V.; Krizkova S.; Hrabeta J.; Eckschlager T.; Stiborova M.; Kizek R. An electrochemical study of interaction of an anticancer alkaloid ellipticine with DNA, Chim. Oggi-Chem. Today, 2010, 28(5 Suppl S), 15-17.
85. Miller C.M.; McCarthy F.O. Isolation, biological activity and synthesis of the natural product ellipticine and related pyridocarbazoles, RSC Advances, 2012, 2(24), 8883-89188
86. Chadwick M.; Silveira D.M.; Platz B.R.; Hayes D. Comparative physiological disposition of ellipticine in several animal species after intravenous administration, Drug Metab. Dispos., 1978, 6(5), 528-541.
87. Branfam A.R.; Bruni R.J.; Reihold V.N.; Silveira D.M.; Chadwick M.; Yesair D.W. Characterization of metabolites of ellipticine in rat bile, Drug Metab. Dispos., 1978, 6(5), 542-548.
88. Ismail M.A.; Sanders K.J.; Fennell G.C.; Latham H.C.; Wormell P.; Rodger A. Spectroscopic studies of 9-hydroxyellipticine binding to DNA, Biopolymers, 1998, 46(3), 127-143.
89. Jain S. C.; Bhandary K. K.; Sobell H.M. Visualization of drug - nucleic acid interactions at atomic resolution. VI. Structure of two drug - dinucleoside monophosphate crystalline complexes, ellipticine - 5-iodocytidylyy (3'-5') guanosine and 3,5,6,8-tetramethyl-Nmethyl phenanthrolinium - 5-iodocytidylyl (3'-5') guanosine, J. Mol. Biol., 1979, 135(4), 813-840.
90. Ross W.E.; Bradley M.O. DNA double-stranded breaks in mammalian cells after exposure to intercalating agents, Bioch. Biophys. Acta, 1981, 654(1), 129-134.
91. Tewey K.; Rowe T.; Yang L.; Halligan B.; Liu L. Adriamycininduced DNA damage mediated by mammalian DNA topoisomerase II. Science, 1984, 226(4673), 466-468.
92. Fossé P.; René B.; Le Bret M.; Paoletti C.; Saucier J.M. Sequence requirements for mammalian topoisomerase II mediated DNA cleavage stimulated by an ellipticine derivative, Nucleic Acids Res., 1991, 19(11), 2861-2868.
93. Fossé P.; René B.; Charra M.; Paoletti C.; Saucier J.M. Stimulation of topoisomerase II-mediated DNA cleavage by ellipticine derivatives: structure-activity relationships, Mol. Pharmacol., 1992, 42(4), 590-595.
94. Auclair C.; Paoletti C. Bioactivation of the antitumor drugs 9- hydroxyellipticine and derivatives by a peroxidase-hydrogen peroxide system, J. Med. Chem., 1981, 24(3), 289-295.
95. Bernadou J.; Meunier G.; Paoletti C.; Meunier B. Ortho-quinone formation in the biochemical oxidation of the anti-tumor drug N2- methyl-9- hydroxyellipticinium acetate, J. Med. Chem., 1983, 26(4), 574-579.
96. Bernadou J.; Bonnafous M.; Labat G.; Loiseau P.; Meunier B. Model systems for metabolism studies - biomimetic oxidation of acetaminophen and ellipticine derivatives with water-soluble metalloporphyrins associated to potassium monopersulfate, Drug Metab. Dispos., 1991, 19(2), 360-365.
97. Dugué B.; Paoletti C.; Meunier B. Covalent binding of antitumor agent N2-methyl-9-hydroxy-ellipticinium acetate (NSC 264137) on RNA and poly A in vitro, Biochem. Biophys. Res. Commun., 1984, 12(2), 416-422.
98. Dugué B.; Auclair C.; Meunier B. Covalent binding of elliptinium acetate (NSC 264137) to nucleic acids of L1210 cells in culture, Cancer Res.., 1986, 46(8), 3828-3833.
99. Kansal V.K.; Funakoshi S.; Mangeney P.; Gillet B.; Guittet E.; Lallemand J.Y.; Potier P. Interaction of nucleosides with antitumoral agents - 9-hydroxy-N2-methylellipticinium acetate and 9- hydroxy-N2-methylolivacinium acetate, Tetrahedron, 1985, 41(22), 5107-5120.
100. Kansal V.K.; Potier P.; Gillet B.; Guittet E.; Lallemand J.Y.; Huynh-Dinh T.; Igolen J. Regioselective and stereoselective alkylation at the 3'-terminal end of ribonucleotides by N2-methyl-9- hydroxyellipticinium acetate - an antitumor agent, Tetrahedron Lett., 1985, 26(22), 2891-2894.
101. Meunier G.; Meunier B. Peroxidase-catalyzed O-demethylation reactions - quinone-imine fromation from 9-methoxyellipticine derivatives, J. Biol. Chem., 1985, 260(19), 10576-10582.
102. Meunier G.; Demontauzon D.; Bernandou J.; Grassy G.; Bonnafous M.; Cros S.; Meunier B. The biooxidation of cyto-toxic ellipticine derivatives - a key to structure-activity relationship studies, Mol. Pharmacol., 1988, 33(1), 93-102.
103. Auclair C.; Dugué B.; Meunier B.; Paoletti C. Peroxidase-catalyzed covalent binding of the antitumor drug N2-methyl-9- hydroxyellipticinium to DNA in vitro, Biochemistry, 1986, 25(6), 1240-1245.
104. Pratviel G.; Bernadou J.; Ha T.; Meunier G.; Cros S.; Meunier B.; Gillet B.; Guitret E. Ribose as the preferential target for the oxidized form of elliptinium acetate in ribonucleos(t)ides - biologicalactivities of the resulting adducts, J. Med. Chem., 1986, 20(8), 1350-1355.
105. Poljaková J.; Forsterová K.; Šulc M.; Frei E.; Stiborová M. Oxidation of ellipticine by peroxidases, Biomed. Pap. Med. Fac. Univ. Palacky Olomouc Czech Repub., 2005, 149(2), 449-453.
106. Poljaková J.; Dračínský M.; Frei E.; Hudeček J., Stiborová M. The effect of pH on peroxidase-mediated oxidation of and DNA-adduct formation by ellipticine, Collect. Czech. Chem. Commun., 2006, 71(8), 1169-1185.
107. Martínek V.; Sklenár J.; Dracínsky M.; Sulc M.; Hofbauerová K.; Bezouska K.; Frei E.; Stiborová M. Glycosylation protects proteins against free radicals generated from toxic xenobiotics, Toxicol. Sci., 2010, 117(2), 59-74.
108. Stiborová M.; Arlt V.M.; Henderson C.J.; Wolf C.R.; Kotrbová V.; Moserová M.; Hudecek J.; Phillips D.H.; Frei E. Role of hepatic cytochromes P450 in bioactivation of the anticancer drug ellipticine: studies with the hepatic NADPH:cytochrome P450 reductase null mouse, Toxicol. Appl. Pharmacol., 2008, 226(3), 318-327.
109. Stiborová M.; Moserová M.; Mrázová B.; Kotrbová V.; Frei E. Role of cytochromes P450 and peroxidases in metabolism of the anticancer drug ellipticine: additional evidence of their contribution to ellipticine activation in rat liver, lung and kidney, Neuro Endocrinol. Lett., 2010, 31(Suppl. 2), 26-35.
110. Stiborová M.; Eckschlager T.; Poljaková J.; Hraběta J.; Adam V.; Kizek R.; Frei E. The synergistic effects of DNA-targeted chemotherapeutics and histone deacetylase inhibitors as therapeutic strategies for cancer treatment, Curr. Med. Chem., 2012, 19(25), 4218-4238.
111. Vranová I.; Moserová M.; Hodek P.; Kizek R.; Frei E.; Stiborová M. The anticancer drug ellipticine induces cytochromes P450 1A1, 1A2 and 3A, cytochrome b5 and NADPH:cytochrome P450 in rat liver, kidney and lung, Int. J. Electrochem. Sci., 2013, 8(2), 1586-1597.
112. Stiborová M.; Borek-Dohalská L.; Aimová D.; Kotrbová V.; Kukacková K.; Janouchová K.; Rupertová M.; Ryslavá H.; Hudecek J.; Frei E. Oxidation pattern of the anticancer drug ellipticine by hepatic microsomes - similarity between human and rat systems, Gen. Physiol. Biophys., 2006, 25(3), 245-261.
113. Hofle G.; Glase N.; Leibold T.; Sefkow M. Epothilone A-D and their thiazole-modified analogs as novel anticancer agents, Pure Appl. Chem., 1999, 71(11), 2019-2024.
114. Yamazaki H.; Gillam E.M.; Dong M.S.; Johnson W.W.; Guengerich F.P.,; Shimada T. Reconstitution of recombinant cytochrome P450 2C10(2C9) and comparison with cytochrome P450 3A4 and other forms: effects of cytochrome P450-P450 and cytochrome P450-b5 interactions, Arch. Biochem. Biophys., 1997, 342(2), 329-337.
115. Yamazaki H.; Shimada T.; Martin M.V.; Guengerich F.P. Stimulation of cytochrome P450 reactions by apo-cytochrome b5: evidence against transfer of heme from cytochrome P450 3A4 to apocytochrome b5 or heme oxygenase, J. Biol. Chem., 2001, 276(33), 30885-30891.
116. Schenkman J.B.; Jansson I. The many roles of cytochrome b5, Pharmacol. Ther., 2003, 97(2), 139-152.
117. Zhang H.; Myshkin E.; Waskell L. Role of cytochrome b5 in catalysis by cytochrome P450 2B4, Biochem. Biophys. Res. Commun., 2005, 338(1), 499-506.
118. Zhang H.; Im S.C.; Waskell L. Cytochrome b5 increases the rate of product formation by cytochrome P450 2B4 and competes with cytochrome P450 reductase for a binding site on cytochrome P450 2B4, J. Biol. Chem., 2007, 282(41), 29766-29776.
119. Kotrbová V.; Aimová D.; Ingr M.; Borek-Dohalská L.; Martínek V.; Stiborová M. Preparation of a biologically active apocytochrome b5 via heterologous expression in Escherichia coli, Protein Expr. Purif., 2009, 66(2), 203-209.
120. Rendic S.; Di Carlo F.J. Human cytochrome P450 enzymes: a status report summarizing their reactions, substrates, inducers, and inhibitors, Drug Metab. Rev., 1997, 29(1-2), 413-580.
121. Rendic S.; Guengerich F.P. Contributions of human enzymes in carcinogen metabolism, Chem. Res. Toxicol., 2012, 25(7), 1316-1383.
122. Moserova M.; Kotrbova V.; Rupertova M.; Naiman K.; Hudecek J.; Hodek P.; Frei E.; Stiborova M. Isolation and partial characterization of the adduct formed by 13-hydroxyellipticine with deoxyguanosine in DNA, Neuro Endocrinol, Lett., 2008, 29(5), 728-732.
123. Glatt H.; Boeing H.; Engelke C.E.; Ma L.; Kuhlow A.; Pabel U.; Pomplun D.; Teubner W.; Meinl W. Human cytosolic sulphotransferases: genetics, characteristics, toxicological aspects, Mutat. Res., 2001, 482(1-2), 27-40.
124. Aust S.; Obrist P.; Klimpfinger M.; Tucek G.; Jäger W.; Thalhammer T. Altered expression of the hormone- and xenobioticmetabolizing sulfotransferase enzymes 1A2 and 1C1 in malignant breast tissue, Int. J. Oncol., 2005, 26(4), 1079-1085.
125. Lin S.S.; Chung J.G.; Lin J.P.; Chuang J.Y.; Chang W.C.; Wu J.Y.; Tyan Y.S. Berberine inhibits arylamine N-acetyltransferase activity and gene expression in mouse leukemia L 1210 cells, Phytomedicine, 2005, 12(5), 351-358.
126. Sim E.; Westwood I.; Fullam E. Arylamine N-acetyltransferases, Expert Opin. Drug Metab.Toxicol., 2007, 3(2), 169-184.
127. Butcher N.J.; Tetlow N.L.; Cheung C.; Broadhurst G.M.; Minchin R.F. Induction of human arylamine N-acetyltransferase type I by androgens in human prostate cancer cells, Cancer Res., 2007, 67(1), 85-92.
128. Murias M.; Miksits M.; Aust S.; Spatzenegger M.; Thalhammer T.; Szekeres T.; Jaeger W. Metabolism of resveratrol in breast cancer cell lines: impact of sulfotransferase 1A1 expression on cell growth inhibition, Cancer Lett., 2008, 261(2), 172-182.
129. Meinl W.; Ebert B.; Glatt H.; Lampen A. Sulfotransferase forms expressed in human intestinal Caco-2 and TC7 cells at varying stages of differentiation and role in benzo[a]pyrene metabolism, Drug Metab. Dispos., 2008, 36(2), 276-283.
130. Shu X.H.; Li H.; Sun X.X.; Wang Q.; Sun Z.; Wu M.L.; Chen X.Y.; Li C.; Kong Q.Y.; Liu J. Metabolic patterns and biotransformation activities of resveratrol in human glioblastoma cells: relevance with therapeutic efficacies, PLoS One, 2011, 6(11), e27484.
131. Stiborová M.; Poljaková J.; Martínková E.; Bořek-Dohalská L.; Eckschlager T.; Kizek R.; Frei E. Ellipticine cytotoxicity to cancer cell lines - a comparative study, Interdiscip. Toxicol., 2011, 4(2), 98-105.
132. Murray G.I.; Weaver R.J.; Paterson P.J.; Ewen S.W.; Melvin W.T.; Burke M.D. Expression of xenobiotic metabolizing enzymes in breast cancer, J. Pathol., 1993, 169(3), 347-353.
133. Murray G.I.; Melvin W.T.; Burke M. Cytochrome P450 expression in tumors, J. Pathol., 1995, 176(3), 323-324.
134. Murray G.I. Taylor M.C.; McFadyen M.C.; McKay J.A.; Greenlee W.F.; Burke M.D.; Melvin W.T. Tumor-specific expression of cytochrome P450 CYP1B1, Cancer Res., 1997, 57(14), 3026-3031.
135. Patterson L.H.; McKeown S.R.; Robson T.; Gallagher R.; Raleigh S.M.; Orr S. Antitumor prodrug development using cytochrome P450 (CYP) mediated activation, Anti-Cancer Drug Design, 1999, 14(6), 473-486.
136. Iscan M.; Klaavuniemi T.; Coban T.; Kapucuoglu N.; Pelkonen O.; Raunio H. The expression of cytochrome P450 enzymes in human breast tumours and normal breast tissue, Breast Cancer Res., Treat., 2001, 70(1), 47-54.
137. Rooney P.H.; Telfer C.; McFadyen M.C.; Melvin W.T.; Murray G.I. The role of cytochrome P450 in cytotoxic bioactivation: future therapeutic directions, Curr. Cancer Drug Targets, 2004, 4(3), 257-265.
138. McFadyen M.C.; Melvin W.T.; Murray G.I. Cytochrome P450 enzymes: novel options for cancer therapeutics, Mol. Cancer Ther., 2004, 3(3), 363-371.
139. McFadyen M.C.; Murray G.I. Cytochrome P450 1B1: a novel anticancer therapeutic target, Future Oncol., 2005, 1(2), 259-2633
140. Haas S.; Pierl C.; Harth V.; Pesch B.; Rabstein S.; Brüning T.; Ko Y.; Hamann U.; Justenhoven C.; Brauch H.; Fischer H.P. Expression of xenobiotic and steroid hormone metabolizing enzymes in human breast carcinomas, Int. J. Cancer, 2006, 119(8), 1785-1791.
141. Yu W.; Chai H.; Li Y.; Zhao H.; Xie X.; Zheng H.; Wang C.; Wang X.; Yang G.; Cai X.; Falck J.R.; Yang J. Increased expression of CYP4Z1 promotes tumor angiogenesis and growth in human breast cancer, Toxicol. Appl. Pharmacol., 2012, 264(1), 73-83.
142. Dipple A.; Khan Q.A.; Page J.E.; Pontén I.; Szeliga J. DNA reactions, mutagenic action and stealth properties of polycyclic aromatic hydrocarbon carcinogens (review), Int. J. Oncol., 1999, 14(1), 103-111.
143. Khan Q.A.; Vousden K.H.; Dipple A. Lack of p53-mediated G1 arrest in response to an environmental carcinogen, Oncology, 1999, 57(3), 258-264.
144. Simões M.L.; Hockley S.L.; Schwerdtle T.; da Costa G.G.; Schmeiser H.H.; Phillips D.H.; Arlt V.M. Gene expression profiles modulated by the human carcinogen aristolochic acid I in human cancer cells and their dependence on TP53, Toxicol. Appl. Pharmacol., 2008, 232(1), 86-98.
145. Hockley S.L.; Arlt V.M.; Brewer D.; Giddings I.; Phillips D.H. Time- and concentration-dependent changes in gene expression induced by benzo(a)pyrene in two human cell lines, MCF-7 and HepG2, BMC Genomics, 2006, 7, 260.
146. Hamouchene H.; Arlt V.M.; Giddings I.; Phillips D.H. Influence of cell cycle on responses of MCF-7 cells to benzo[a]pyrene, BMC Genomics, 2011, 12, 333.
147. Senturk E.; Manfredi J.J. p53 and cell cycle effects after DNA damage, Methods. Mol. Biol., 2013, 962, 49-611
148. Broschard T.H.; Wiessler M.; von der Lieth C.W.; Schmeiser H.H. Translesional synthesis on DNA templates containing sitespecifically placed deoxyadenosine and deoxyguanosine adducts formed by the plant carcinogen aristolochic acid, Carcinogenesis, 1994, 15(10), 2331-2340.
149. Ross W.P.; Kaina B. DNA damage-induced cell death by apoptosis, Trends Mol. Med., 2006, 12(1), 440-450.
150. Randerath K.; Haglund R.E.; Phillips D.H.; Reddy M.V. 32P-postlabelling analysis of DNA adducts formed in the livers of animals treated with safrole, estragole and other naturally-occurring alkenylbenzenes. I. Adult female CD-1 mice, Carcinogenesis, 1984, 5(12), 1613-1622.
151. Ross J.A.; Nelson G.B.; Wilson K.H.; Rabinowitz J.R.; Galati A.; Stoner G.D.; Nesnow S.; Mass M.J. Adenomas induced by polycyclic aromatic hydrocarbons in strain A/J mouse lung correlate with time-integrated DNA adduct levels, Cancer Res., 1995, 55(5), 1039-1044.
152. Smith B.A.; Fullerton N.F.; Heflich R.H.; Beland F.A. DNA adduct formation and T-lymphocyte mutation induction in F344 rats implanted with tumorigenic doses of 1,6-dinitropyrene, Cancer Res., 1995, 55(11), 2316-2324.
153. Godschalk R.W.L.; Moonen E.J.C.; Schilderman P.A.E.L.; Broekmans W.M.R.; Kleinjans J.C.S.; van Schooten F.J. Exposure-routedependent DNA adduct formation by polycyclic aromatic hydrocarbons, Carcinogenesis, 2000, 21(1), 87-92.
154. Poirier M.C. Chemical-induced DNA damage and human cancer risk, Nat. Rev. Cancer, 2004, 4(8), 630-637.
155. Naiman K.; Dračínský M.; Hodek P.; Martínková M.; Schmeiser H.H.; Frei E.; Stiborová M. Formation and persistence of DNA adducts of the carcinogenic environmental pollutant o-anisidine in rats and structural characterization of the major adduct, Toxicol. Sci., 2012, 127(2), 348-359.
156. Aimová D.; Svobodová L.; Kotrbová V.; Mrázová B.; Hodek P.; Hudeček J.; Václaví ková R.; Frei E.; Stiborová M. The anticancer drug ellipticine is a potent inducer of rat cytochromes P450 1A1 and 1A2, thereby modulating its own metabolism, Drug Metab. Dispos., 2007, 35(10), 1926-1934.
157. Bořek-Dohalská L.; Poljaková J.; Rupertová M.; Frei E.; Stiborová M. Pretreatment of human breast adenocarcinoma MCF-7 cells by ellipticine potentiates its own cytotoxicity, Interdiscip. Toxicol., 2009, 2(2), 94s.
158. Fernandez N.; Roy M.; Lesca P. Binding characteristics of Ah receptors from rats and mice before and after separation from hepatic cytosols. 7-Hydroxyellipticine as a competitive antagonist of cytochrome P-450 induction, Eur. J. Biochem., 1988, 172(3), 585-592.
159. Gasiewicz T.A.; Kende R.S.; Rucci G.; Whitney B.; Willey J.J. Analysis of structural requirements for Ah receptor antagonist activity: Ellipticines, flavones, and related compounds, Biochem. Pharmacol., 1996, 52(11), 1787-1830.
160. Aimová D.; Stiborová M. Antitumor drug ellipticine inhibits the activities of rat hepatic cytochromes P450, Biomed. Pap. Med. Fac. Univ. Palacky Olomouc Czech Repub., 2005, 149(2), 437-440.
161. Chang C.Y.; Puga A. Constitutive activation of the aromatic hydrocarbon receptor, Mol. Cell. Biol., 1998, 18(1), 525-535.
162. Schlaifer D.; Meyer K.; Muller C.; Attal M.; Smith M.T.; Tamaki S.; Weimels J.; Pris J.; Jaffrezou J.P.; Laurent G.; Myers C.E. Antisense inhibition of myeloperoxidase increases the sensitivity of the HL-60 cell line to vincristine, Leukemia, 1994, 8(2), 289-291.
163. Lübbert M.; Miller C.W.; Koeffler H.P. Changes of DNA methylation and chromatin structure in the human myeloperoxidase gene during myeloid differentiation, Blood, 1991, 78(2), 345-356.
164. Hoy A.; Leininger-Muller B.; Jolivalt C.; Siest G. Effect of apolipoprotein E on cell viability in a human neuroblastoma cell line: influence of oxidation and lipid-association. Neurosci. Lett., 2000, 285(3), 173-176.
165. Williams J.A.; Phillips D.H. Mammary expression of xenobiotic metabolizing enzymes and their potential role in breast cancer, Cancer Res., 2000, 60(17), 4667-4677.
166. Soslow R.A.; Dannenberg A.J.; Rush D.; Woemer B.M.; Khan K.M.; Masferrerer J.; Koki A. I. COX-2 is expressed in human pulmonary, colonic, and mammary tumors, Cancer, 2000, 89(12), 2637-2645.
167. Matsuo M.; Yonemitsu N.; Zaitsu M.; Ishii K.; Hamasaki Y.; Fukuyama K.; Tabuchi K.; Miyazaki S. Expression of prostaglandin H synthase-2 in human brain tumors, Acta Neuropathol., 2001, 102(2), 181-187.
168. Schmelz K.; Sattler N.; Wagner M.; Lubbert M.; Dorken B.; Tamm I. Induction of gene expression by 5-aza-2'-deoxycytidine in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) but not epithelial cells by DANN-methylation-dependent and - independent mechanisms, Leukemia, 2005, 19(1), 103-111.
169. Shono T.; Tofilon P.J.; Bruner J.M.; Owolabi O.; Lang F.F. Cyclooxygenase- 2 expression in human gliomas: Prognostic significance and molecular correlations, Cancer Res., 2001, 61(11), 4375-4381.
170. Peng J.P.; Su C.Y.; Chang H.C.; Chai C.Y.; Hung W.C. Overexpression of cyclo-oxygenase 2 in squamous cell carcinoma of the hypopharynx, Human Pathol., 2002, 33(1), 100-104.
171. Castilla E.A.; Prayson R.A.; Kanner A.A.; Rybicky L.A.; Tubbs R.R.; Vogelbaum M.A.; Barnett G.H. Cyclooxygenase-2 in oligodendroglial neoplasms, Cancer, 2003, 98(7), 1465-1472.
172. Ludwig-Muller J.; Tokalov S.V.; Franz A.; Gutzeit H.O. Quercetin metabolism in vital and apoptotic human leukaemia cells, Biol. Chem., 2005, 386(3), 279-283.
173. Kirschenbaum A.; Klausner A.P.; Lee R.; Unger P.; Yao S.; Kiu X.H.; Levine A.C. Expression of cyclooxygenase-1 and cyclooxygenase- 2 in the human prostate, Urology, 2000, 56(4), 671-676.
174. Donaghy M.J.; Stanforch, S.P. Nucleophilic addition of fused benzimidazole N-oxide, Tetrahedron, 1999, 55(5), 1441-1448.