Metabolic transformation of antitumor acridinone C-1305 but not C-1311 via selective cellular expression of UGT1A10 increases cytotoxic response: Implications for clinical use

Drug Metabolism and Disposition

Volumn 41, Issue 2, 2013, Pages 414-421

  Pawlowska, Monika ^a   Chu, Rong ^b   Fedejko Kap, Barbara ^a   Augustin, Ewa ^a   Mazerska, Zofia ^a   Radominska Pandya, Anna ^b   Chambers, Timothy C ^b  

^a GDANSK UNIVERSITY OF TECHNOLOGY   (Poland)

^b UNIVERSITY OF ARKANSAS FOR MEDICAL SCIENCES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

5 DIETHYLAMINOETHYLAMINO 8 HYDROXYIMIDAZOACRIDINONE; 5 DIMETHYLAMINOPROPYLAMINO 8 HYDROXYTRIAZOLOACRIDINONE; ACRIDONE DERIVATIVE; ANTINEOPLASTIC AGENT; C 1305; GLUCURONIDE; GLUCURONOSYLTRANSFERASE; GLUCURONOSYLTRANSFERASE 1A10; GLUCURONOSYLTRANSFERASE 2B4; IMIDACRINE; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; ARTICLE; CELL STRAIN; CELL STRAIN KB 3; CONTROLLED STUDY; DRUG CYTOTOXICITY; DRUG DETOXIFICATION; DRUG GLUCURONIDATION; DRUG MECHANISM; DRUG STRUCTURE; DRUG TRANSFORMATION; ENZYME ACTIVITY; HELA CELL; HUMAN; HUMAN CELL; PRIORITY JOURNAL; PROTEIN EXPRESSION;

ACRIDINES; AMINOACRIDINES; ANTINEOPLASTIC AGENTS; BIOTRANSFORMATION; CELL SURVIVAL; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; GLUCURONIDES; GLUCURONOSYLTRANSFERASE; HELA CELLS; HUMANS; INHIBITORY CONCENTRATION 50; TRANSFECTION; TRIAZOLES; UTERINE CERVICAL NEOPLASMS;

EID: 84872731735     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.112.047811     Document Type: Article

References (27)

1. Augustin E, Mo-s-Rompa A, Skwarska A, Witkowski JM, and Konopa J (2006) Induction of G2/M phase arrest and apoptosis of human leukemia cells by potent antitumor triazoloacridinone C-1305. Biochem Pharmacol 72:1668-1679. (Pubitemid 44765001)
2. Burger AM, Double JA, Konopa J, and Bibby MC (1996) Preclinical evaluation of novel imidazoacridinone derivatives with potent activity against experimental colorectal cancer. Br J Cancer 74:1369-1374. (Pubitemid 26370726)
3. Capizzi RL, Roman LA, Tjulandin S, Smirnova I, Manikhas A, Paterson JS, Major A, Lundberg AS, and Fumoleau P (2008) Phase II trial of C1311, a novel inhibitor of topoisomerase II in advanced breast cancer. J Clin Oncol 26:1055.
4. Cholody WM, Horowska B, Paradziej-Lukowicz J, Martelli S, and Konopa J (1996) Structureactivity relationship for antineoplastic imidazoacridinones: synthesis and antileukemic activity in vivo. J Med Chem 39:1028-1032. (Pubitemid 26082935)
5. Cholody WM, Martelli S, and Konopa J (1990a) 8-Substituted 5-[(aminoalkyl)amino]-6H-vtriazolo[ 4,5,1-de]acridin-6-ones as potential antineoplastic agents: synthesis and biological activity. J Med Chem 33:2852-2856. (Pubitemid 20312155)
6. Cholody WM, Martelli S, Paradziej-Lukowicz J, and Konopa J (1990b) 5-[(Aminoalkyl)amino] imidazo[4,5,1-de]acridin-6-ones as a novel class of antineoplastic agents: synthesis and biological activity. J Med Chem 33:49-52. (Pubitemid 20038169)
7. Davis FM, Tsao TY, Fowler SK, and Rao PN (1983) Monoclonal antibodies to mitotic cells. Proc Natl Acad Sci USA 80:2926-2930.
8. Dziegielewski J and Konopa J (1996) Interstrand crosslinking of DNA induced in tumor cells by a new group of antitumor imidazoacridinones. Proc Am Assoc Cancer Res 37:410.
9. Dziegielewski J, Slusarski B, Konitz A, Skladanowski A, and Konopa J (2002) Intercalation of imidazoacridinones to DNA and its relevance to cytotoxic and antitumor activity. Biochem Pharmacol 63:1653-1662. (Pubitemid 34458004)
10. Fedejko-Kap B, Bratton SM, Finel M, Radominska-Pandya A, and Mazerska Z (2012) The role of human UDP-glucuronosyltransferases in the biotransformation of the triazoloacridinone and imidazoacridinone antitumor agents C-1305 and C-1311: highly selective substrates for UGT1A10. Drug Metab Dispos 40:1736-1743.
11. Fedejko-Kap B, Niemira M, Radominska-Pandya A, and Mazerska Z (2011) Flavin monooxygenases, FMO1 and FMO3, not cytochrome P450 isoenzymes, contribute to metabolism of anti-tumour triazoloacridinone, C-1305, in liver microsomes and HepG2 cells. Xenobiotica 41: 1044-1055.
12. Gosland M, Tsuboi C, Hoffman T, Goodin S, and Vore M (1993) 17 beta-estradiol glucuronide: an inducer of cholestasis and a physiological substrate for the multidrug resistance transporter. Cancer Res 53:5382-5385. (Pubitemid 23342154)
13. Isambert N, Campone M, Bourbouloux E, Drouin M, Major A, Yin W, Loadman P, Capizzi R, Grieshaber C, and Fumoleau P (2010) Evaluation of the safety of C-1311 (SYMADEX) administered in a phase 1 dose escalation trial as a weekly infusion for 3 consecutive weeks in patients with advanced solid tumours. Eur J Cancer 46:729-734.
14. Koba M and Konopa J (2007) Interactions of antitumor triazoloacridinones with DNA. Acta Biochim Pol 54:297-306. (Pubitemid 47057873)
15. Ku-snierczyk H, Cholody WM, Paradziej-Lukowicz J, Radzikowski C, and Konopa J (1994) Experimental antitumor activity and toxicity of the selected triazolo- and imidazoacridinones. Arch Immunol Ther Exp (Warsz) 42:415-423.
16. Lemke K, Poindessous V, Skladanowski A, and Larsen AK (2004) The antitumor triazoloacridone C-1305 is a topoisomerase II poison with unusual properties. Mol Pharmacol 66:1035-1042. (Pubitemid 39319476)
17. Livak KJ and Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-D D C(T)) Method. Methods 25:402-408. (Pubitemid 34164012)
18. Mazerska Z, Dziegielewski J, and Konopa J (2001) Enzymatic activation of a new antitumour drug, 5-diethylaminoethylamino-8-hydroxyimidazoacridinone, C-1311, observed after its intercalation into DNA. Biochem Pharmacol 61:685-694. (Pubitemid 32239421)
19. Mazerska Z, Sowinski P, and Konopa J (2003) Molecular mechanism of the enzymatic oxidation investigated for imidazoacridinone antitumor drug, C-1311. Biochem Pharmacol 66:1727-1736. (Pubitemid 37249317)
20. Potega A, Dabrowska E, Niemira M, Kot-Wasik A, Ronseaux S, Henderson CJ, Wolf CR, and Mazerska Z (2011) The imidazoacridinone antitumor drug, C-1311, is metabolized by flavin monooxygenases but not by cytochrome P450s. Drug Metab Dispos 39:1423-1432.
21. Ritter JK (2000) Roles of glucuronidation and UDP- glucuronosyltransferases in xenobiotic bioactivation reactions. Chem Biol Interact 129:171-193. (Pubitemid 32061059)
22. Sallustio BC, Degraaf YC, Weekley JS, and Burcham PC (2006) Bioactivation of carboxylic acid compounds by UDP-glucuronosyltransferases to DNA-damaging intermediates: role of glycoxidation and oxidative stress in genotoxicity. Chem Res Toxicol 19:683-691. (Pubitemid 43800985)
23. Skladanowski A, Plisov SY, Konopa J, and Larsen AK (1996) Inhibition of DNA topoisomerase II by imidazoacridinones, new antineoplastic agents with strong activity against solid tumors. Mol Pharmacol 49:772-780. (Pubitemid 26149906)
24. Skwarska A, Augustin E, and Konopa J (2007) Sequential induction of mitotic catastrophe followed by apoptosis in human leukemia MOLT4 cells by imidazoacridinone C-1311. Apoptosis 12:2245-2257. (Pubitemid 350077255)
25. Thomas AL, Anthoney A, Scott E, Ahmed S, Lundberg AS, Major A, Capizzi RL, and Twelves CJ (2008) C-1311, a novel inhibitor of FLT3 and topoisomerase II: a phase 1 trial of once every three week schedule in patients with advanced solid tumors. J Clin Oncol 26:S2576.
26. van Dorp EL, Romberg R, Sarton E, Bovill JG, and Dahan A (2006) Morphine-6-glucuronide: morphine's successor for postoperative pain relief? Anesth Analg 102:1789-1797. (Pubitemid 43799857)
27. Wittwer E and Kern SE (2006) Role of morphine's metabolites in analgesia: concepts and controversies. AAPS J 8:E348-E352. (Pubitemid 43840593)