Cytochrome P450-mediated biotransformation of sorafenib and its N-oxide metabolite: Implications for cell viability and human toxicity

Chemical Research in Toxicology

Volumn 28, Issue 1, 2015, Pages 92-102

  Gillani, Tina B ^a   Rawling, Tristan ^b   Murray, Michael ^a  

^a UNIVERSITY OF SYDNEY   (Australia)

^b UNIVERSITY OF TECHNOLOGY SYDNEY   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE TRIPHOSPHATE; CYTOCHROME P450; CYTOCHROME P450 1A1; CYTOCHROME P450 2B6; CYTOCHROME P450 3A4; N OXIDE; OXIDE; SORAFENIB; UNCLASSIFIED DRUG; ANTINEOPLASTIC AGENT; CARBANILAMIDE DERIVATIVE; CYTOCHROME P450 INHIBITOR; NICOTINAMIDE; PROTEIN KINASE INHIBITOR;

ADOLESCENT; ADULT; AGED; ARTICLE; CELL CYCLE G0 PHASE; CELL CYCLE G1 PHASE; CELL CYCLE G2 PHASE; CELL CYCLE M PHASE; CELL CYCLE PROGRESSION; CELL CYCLE S PHASE; CELL VIABILITY; CHILD; CONTROLLED STUDY; CYTOTOXICITY; DRUG METABOLISM; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TRANSFORMATION; FEMALE; HUMAN; HUMAN CELL; HUMAN EXPERIMENT; MALE; OXIDATION; ANALOGS AND DERIVATIVES; BIOTRANSFORMATION; CELL CYCLE; CELL SURVIVAL; DRUG EFFECTS; HEPG2 CELL LINE; LIVER MICROSOME; METABOLISM;

ANTINEOPLASTIC AGENTS; BIOTRANSFORMATION; CELL CYCLE; CELL SURVIVAL; CYTOCHROME P-450 ENZYME INHIBITORS; CYTOCHROME P-450 ENZYME SYSTEM; HEP G2 CELLS; HUMANS; MICROSOMES, LIVER; NIACINAMIDE; PHENYLUREA COMPOUNDS; PROTEIN KINASE INHIBITORS;

EID: 84922462919     PISSN: 0893228X     EISSN: 15205010     Source Type: Journal    
DOI: 10.1021/tx500373g     Document Type: Article

References (53)

1. Escudier, B., Eisen, T., Stadler, W. M., Szczylik, C., Oudard, S., Siebels, M., Negrier, S., Chevreau, C., Solska, E., Desai, A. A., Rolland, F., Demkow, T., Hutson, T. E., Gore, M., Freeman, S., Schwartz, B., Shan, M., Simantov, R., and Bukowski, R. M. (2007) Sorafenib in advanced clear-cell renal-cell carcinoma N. Engl. J. Med. 356, 125-134
2. Llovet, J. M., Ricci, S., Mazzaferro, V., Hilgard, P., Gane, E., Blanc, J. F., de Oliveira, A. C., Santoro, A., Raoul, J. L., Forner, A., Schwartz, M., Porta, C., Zeuzem, S., Bolondi, L., Greten, T. F., Galle, P. R., Seitz, J. F., Borbath, I., Häussinger, D., Giannaris, T., Shan, M., Moscovici, M., Voliotis, D., and Bruix, J. (2008) Sorafenib in advanced hepatocellular carcinoma N. Engl. J. Med. 359, 378-390
3. Keating, G. M. and Santoro, A. (2009) Sorafenib: a review of its use in advanced hepatocellular carcinoma Drugs 69, 223-240
4. Fairfax, B. P., Pratap, S., Roberts, I. S., Collier, J., Kaplan, R., Meade, A. M., Ritchie, A. W., Eisen, T., Macaulay, V. M., and Protheroe, A. (2012) Fatal case of sorafenib-associated idiosyncratic hepatotoxicity in the adjuvant treatment of a patient with renal cell carcinoma BMC Cancer 12, 590
5. Strumberg, D., Clark, J. W., Awada, A., Moore, M. J., Richly, H., Hendlisz, A., Hirte, H. W., Eder, J. P., Lenz, H. J., and Schwartz, B. (2007) Safety, pharmacokinetics, and preliminary antitumor activity of sorafenib: a review of four phase I trials in patients with advanced refractory solid tumors Oncologist 12, 426-437
6. Ghassabian, S., Rawling, T., Zhou, F., Doddareddy, M. R., Tattam, B. N., Hibbs, D. E., Edwards, R. J., Cui, P. H., and Murray, M. (2012) Role of human CYP3A4 in the biotransformation of sorafenib to its major oxidized metabolites Biochem. Pharmacol. 84, 215-223
7. Minami, H., Kawada, K., Ebi, H., Kitagawa, K., Kim, Y. I., Araki, K., Mukai, H., Tahara, M., Nakajima, H., and Nakajima, K. (2008) Phase I and pharmacokinetic study of sorafenib, an oral multikinase inhibitor, in Japanese patients with advanced refractory solid tumors Cancer Sci. 99, 1492-1498
8. Cui, P. H., Rawling, T., Gillani, T. B., Bourget, K., Wang, X. S., Zhou, F., and Murray, M. (2013) Anti-proliferative actions of N ′-desmethylsorafenib in human breast cancer cells Biochem. Pharmacol. 86, 419-427
9. Rawling, T., McDonagh, A. M., Tattam, B., and Murray, M. (2012) Synthesis of unsymmetrical biaryl ureas from N- carbamoylimidazoles: kinetics and application Tetrahedron 68, 6065-6070
10. Yasukochi, Y. and Masters, B. S. (1976) Some properties of a detergent-solubilized NADPH-cytochrome c (cytochrome P-450) reductase purified by biospecific affinity chromatography J. Biol. Chem. 251, 5337-5344
11. Murray, M. (1991) In vitro and in vivo studies of the effect of vitamin E on microsomal cytochrome P450 in rat liver Biochem. Pharmacol. 42, 2107-2114
12. Guengerich, F. P., Wang, P., and Mason, P. S. (1981) Immunological comparison of rat, rabbit, and human liver NADPH-cytochrome P-450 reductases Biochemistry 20, 2379-2385
13. Sundberg, R. J. and Jiang, S. (1997) Improved procedures for preparation of 4-hydroxy- and 4-methoxy-2-aminopyridines Org. Prep. Proced. Int. 29, 117-122
14. Bankston, D., Dumas, J., Natero, R., Riedl, B., Monahan, M. K., and Sibley, R. (2002) A scaleable synthesis of BAY 43-9006: a potent Raf kinase inhibitor for the treatment of cancer Org. Process Res. Dev. 6, 777-781
15. Varlet, D., Fourmaintraux, E., Depreux, P., and Lesieur, D. (2000) Synthesis of 4-[4′-(N, N -dimethylsulfamoyl)piperazin-1-yl]pyridine derivatives as potential sorbitol dehydrogenase inhibitors Heterocycles 53, 797-804
16. Murray, M. and Field, S. L. (1992) Inhibition and metabolite complexation of rat hepatic microsomal cytochrome P450 by tricyclic antidepressants Biochem. Pharmacol. 43, 2065-2071
17. Bradford, M. M. (1976) Rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding Anal. Biochem. 72, 248-254
18. Prough, R. A., Burke, M. D., and Mayer, R. T. (1978) Direct fluorometric methods for measuring mixed function oxidase activity Methods Enzymol. 52, 372-377
19. Nebot, N., Crettol, S., d'Esposito, F., Tattam, B., Hibbs, D. E., and Murray, M. (2010) Participation of CYP2C8 and CYP3A4 in the N -demethylation of imatinib in human hepatic microsomes Br. J. Pharmacol. 161, 1059-1069
20. Zhang, W. V., d'Esposito, F., Edwards, R. J., Ramzan, I., and Murray, M. (2008) Inter-individual variation in relative CYP1A2/3A4 phenotype influences susceptibility of clozapine oxidation to CYP-specific inhibition in human hepatic microsomes Drug Metab. Dispos. 36, 2547-2555
21. Babić, Ž., Crkvenčić, M., Rajić, Z., Mikecin, A. M., Kralj, M., Balzarini, J., Petrova, M., Vanderleyden, J., and Zorc, B. (2012) New sorafenib derivatives: synthesis, antiproliferative activity against tumour cell lines and antimetabolic evaluation Molecules 17, 1124-1137
22. von Moltke, L. L., Greenblatt, D. J., Court, M. H., Duan, S. X., Harmatz, J. S., and Shader, R. I. (1995) Inhibition of alprazolam and desipramine hydroxylation in vitro by paroxetine and fluvoxamine: comparison with other selective serotonin reuptake inhibitor antidepressants J. Clin. Psychopharmacol. 15, 125-131
23. Reardon, D. A., Vredenburgh, J. J., Desjardins, A., Peters, K., Gururangan, S., Sampson, J. H., Marcello, J., Herndon, J. E., II, McLendon, R. E., Janney, D., Friedman, A. H., Bigner, D. D., and Friedman, H. S. (2011) Effect of CYP3A-inducing anti-epileptics on sorafenib exposure: results of a phase II study of sorafenib plus daily Temozolomide in adults with recurrent glioblastoma J. Neuro-Oncol. 101, 57-66
24. Gomo, C., Coriat, R., Faivre, L., Mir, O., Ropert, S., Billemont, B., Dauphin, A., Tod, M., Goldwasser, F., and Blanchet, B. (2011) Pharmacokinetic interaction involving sorafenib and the calcium-channel blocker felodipine in a patient with hepatocellular carcinoma Invest. New Drugs 29, 1511-1514
25. Sem, D. S. and Kasper, C. B. (1993) Enzyme-substrate binding interactions of NADPH-cytochrome P-450 oxidoreductase characterized with pH and alternate substrate/inhibitor studies Biochemistry 32, 11539-11547
26. Kuntzman, R., Phillips, A., Tsai, I., Klutch, A., and Burns, J. J. (1967) N -Oxide formation: a new route for inactivation of the antihistaminic chlorcyclizine J. Pharmacol. Exp. Ther. 155, 337-344
27. Coccia, P. F. and Westerferd, W. W. (1967) The metabolism of chlorpromazine by liver microsomal enzyme systems J. Pharmacol. Exp. Ther. 157, 446-458
28. Dajani, R. M., Gorrod, J. W., and Beckett, A. H. (1975) In vitro hepatic and extra-hepatic reduction of (-)-nicotine-1′- N -oxide in rats Biochem. Pharmacol. 24, 109-117
29. Bickel, M. H. (1972) Liver metabolic reactions: tertiary amine N -dealkylation, tertiary amine N -oxidation, N -oxide reduction, and N -oxide N -dealkylation. I. Tricyclic tertiary amine drugs Arch. Biochem. Biophys. 148, 54-62
30. Iwasaki, K., Noguchi, H., Kato, R., Imai, Y., and Sato, R. (1977) Reduction of tertiary amine N -oxide by purified cytochrome P-450 Biochem. Biophys. Res. Commun. 77, 1143-1149
31. Parte, P. and Kupfer, D. (2005) Oxidation of tamoxifen by human flavin-containing monooxygenase (FMO) 1 and FMO3 to tamoxifen- N -oxide and its novel reduction back to tamoxifen by human cytochromes P450 and hemoglobin Drug Metab. Dispos. 33, 1446-1452
32. Sugiura, M., Iwasaki, K., Noguchi, H., and Kato, R. (1974) Evidence for the involvement of cytochrome P-450 in tiaramide N -oxide reduction Life Sci. 15, 1433-1442
33. Skalova, L., Nobilis, M., Szotakova, B., Wsol, V., Kubicek, V., Baliharova, V., and Kvasnickova, E. (2000) Effect of substituents on microsomal reduction of benzo(c)fluorene N -oxides Chem.-Biol. Interact. 126, 185-200
34. Seto, Y. and Guengerich, F. P. (1993) Partitioning between N-dealkylation and N -oxygenation in the oxidation of N, N -dialkylarylamines catalyzed by cytochrome P450 2B1 J. Biol. Chem. 268, 9986-9997
35. Patterson, L. H. (1993) Rationale for the use of aliphatic N -oxides of cytotoxic anthraquinones as prodrug DNA binding agents: a new class of bioreductive agent Cancer Metastasis Rev. 12, 119-134
36. Goeptar, R. A., Scheerens, H., and Vermeulen, N. P. E. (1995) Oxygen and xenobiotic reductase activities of cytochrome P450 Crit. Rev. Toxicol. 25, 25-65
37. Mellor, H. R., Bell, A. R., Valentin, J. P., and Roberts, R. R. (2011) Cardiotoxicity associated with targeting kinase pathways in cancer Toxicol. Sci. 120, 14-32
38. Azad, N. S., Aragon-Ching, J. B., Dahut, W. L., Gutierrez, M., Figg, W. D., Jain, L., Steinberg, S. M., Turner, M. L., Kohn, E. C., and Kong, H. H. (2009) Hand-foot skin reaction increases with cumulative sorafenib dose and with combination anti-vascular endothelial growth factor therapy Clin. Cancer Res. 15, 1411-1416
39. Yu, C., Bruzek, L. M., Meng, X. W., Gores, G. J., Carter, C. A., Kaufmann, S. H., and Adjei, A. A. (2005) The role of Mcl-1 downregulation in the proapoptotic activity of the multikinase inhibitor BAY 43-9006 Oncogene 24, 6861-6869
40. Chiou, J. F., Tai, C. J., Wang, Y. H., Liu, T. Z., Jen, Y. M., and Shiau, C. Y. (2009) Sorafenib induces preferential apoptotic killing of a drug- and radio-resistant Hep G2 cells through a mitochondria-dependent oxidative stress mechanism Cancer Biol. Ther. 8, 1904-1913
41. Coriat, R., Nicco, C., Chereau, C., Mir, O., Alexandre, J., Ropert, S., Weill, B., Chaussade, S., Goldwasser, F., and Batteux, F. (2012) Sorafenib-induced hepatocellular carcinoma cell death depends on reactive oxygen species production in vitro and in vivo Mol. Cancer Ther. 11, 2284-2293
42. Wang, R., Xia, L., Gabrilove, J., Waxman, S., and Jing, Y. (2013) Down-regulation of Mcl-1 through GSK-3β activation contributes to arsenic trioxide-induced apoptosis in acute myeloid leukemia cells Leukemia 27, 315-324
43. Locatelli, S. L., Cleris, L., Stirparo, G. G., Tartari, S., Saba, E., Pierdominici, M., Malorni, W., Carbone, A., Anichini, A., and Carlo-Stella, C. (2014) BIM upregulation and ROS-dependent necroptosis mediate the antitumor effects of the HDACi Givinostat and Sorafenib in Hodgkin lymphoma cell line xenografts Leukemia 28, 1861-1871
44. Chen, L., Gong, Q., Stice, J. P., and Knowlton, A. A. (2009) Mitochondrial OPA1, apoptosis, and heart failure Cardiovasc. Res. 84, 91-99
45. Zhao, X., Tian, C., Puszyk, W. M., Ogunwobi, O. O., Cao, M., Wang, T., Cabrera, R., Nelson, D. R., and Liu, C. (2013) OPA1 down-regulation is involved in sorafenib-induced apoptosis in hepatocellular carcinoma Lab. Invest. 93, 8-19
46. Will, Y., Dykens, J. A., Nadanaciva, S., Hirakawa, B., Jamieson, J., Marroquin, L. D., Hynes, J., Patyna, S., and Jessen, B. A. (2008) Effect of the multitargeted tyrosine kinase inhibitors imatinib, dasatinib, sunitinib, and sorafenib on mitochondrial function in isolated rat heart mitochondria and H9c2 cells Toxicol. Sci. 106, 153-161
47. Fiume, L., Manerba, M., Vettraino, M., and Di Stefano, G. (2011) Effect of sorafenib on the energy metabolism of hepatocellular carcinoma cells Eur. J. Pharmacol. 670, 39-43
48. Wan, J., Liu, T., Mei, L., Li, J., Gong, K., Yu, C., and Li, W. (2013) Synergistic antitumour activity of sorafenib in combination with tetrandrine is mediated by reactive oxygen species (ROS)/Akt signaling Br. J. Cancer 109, 342-350
49. Bull, V. H., Rajalingam, K., and Thiede, B. (2012) Sorafenib-induced mitochondrial complex I inactivation and cell death in human neuroblastoma cells J. Proteome Res. 11, 1609-1620
50. Rahmani, M., Davis, E. M., Crabtree, T. R., Habibi, J. R., Nguyen, T. K., Dent, P., and Grant, S. (2007) The kinase inhibitor sorafenib induces cell death through a process involving induction of endoplasmic reticulum stress Mol. Cell. Biol. 27, 5499-5513
51. Yi, P., Higa, A., Taouji, S., Bexiga, M. G., Marza, E., Arma, D., Castain, C., Le Bail, B., Simpson, J. C., Rosenbaum, J., Balabaud, C., Bioulac-Sage, P., Blanc, J. F., and Chevet, E. (2012) Sorafenib-mediated targeting of the AAA+ ATPase p97/VCP leads to disruption of the secretory pathway, endoplasmic reticulum stress, and hepatocellular cancer cell death Mol. Cancer Ther. 11, 2610-2620
52. Kane, R. C., Farrell, A. T., Madabushi, R., Booth, B., Chattopadhyay, S., Sridhara, R., Justice, R., and Pazdur, R. (2009) Sorafenib for the treatment of unresectable hepatocellular carcinoma Oncologist 14, 95-100
53. Boudou-Rouquette, P., Narjoz, C., Golmard, J. L., Thomas-Schoemann, A., Mir, O., Taieb, F., Durand, J. P., Coriat, R., Dauphin, A., Vidal, M., Tod, M., Loriot, M. A., Goldwasser, F., and Blanchet, B. (2012) Early sorafenib-induced toxicity is associated with drug exposure and UGTIA9 genetic polymorphism in patients with solid tumors: a preliminary study PLoS One 7, e42875