In vivo antitumor activity and host toxicity of methoxymorpholinyl doxorubicin: Role of cytochrome P450 3A

Cancer Research

Volumn 60, Issue 12, 2000, Pages 3232-3238

  Quintieri, Luigi ^a   Rosato, Antonio ^a   Napoli, Eleonora ^a   Sola, Francesco ^b   Geroni, Cristina ^b   Floreani, Maura ^a   Zanovello, Paola ^a  

^a UNIVERSITY OF PADOVA   (Italy)

^b PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

16ALPHA CYANOPREGNENOLONE; CYTOCHROME P450 3A; CYTOCHROME P450 INHIBITOR; DOXORUBICIN DERIVATIVE; ELTANOLONE; ERYTHROMYCIN; N DEMETHYLASE; NEMORUBICIN; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; TROLEANDOMYCIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; BONE MARROW SUPPRESSION; CONTROLLED STUDY; CYTOTOXICITY; DRUG MECHANISM; DRUG POTENTIATION; ENZYME ACTIVATION; FEMALE; LETHAL DOSE; LEUKEMIA; LIVER METASTASIS; LIVER MICROSOME; MOUSE; NONHUMAN; PRIORITY JOURNAL;

ANIMALS; ANTI-BACTERIAL AGENTS; ANTIBIOTICS, ANTINEOPLASTIC; ANTINEOPLASTIC AGENTS; ARYL HYDROCARBON HYDROXYLASES; BONE MARROW; COCULTURE TECHNIQUES; CYTOCHROME P-450 CYP3A; CYTOCHROME P-450 ENZYME SYSTEM; DOSE-RESPONSE RELATIONSHIP, DRUG; DOXORUBICIN; ERYTHROMYCIN; FEMALE; LEUKEMIA, EXPERIMENTAL; LIVER; LIVER NEOPLASMS, EXPERIMENTAL; METHYLATION; MICE; MICE, INBRED C57BL; MICE, INBRED DBA; MICROSOMES, LIVER; NADP; NEOPLASM TRANSPLANTATION; NEOPLASMS, EXPERIMENTAL; OXIDOREDUCTASES, N-DEMETHYLATING; PREGNENOLONE CARBONITRILE; PROTEIN SYNTHESIS INHIBITORS; TIME FACTORS; TROLEANDOMYCIN; TUMOR CELLS, CULTURED;

EID: 0034083806     PISSN: 00085472     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (48)

1. Booser, D. J., and Hortobagyi, G. N. Anthracycline antibiotics in cancer therapy. Focus on drug resistance. Drugs, 47: 223-258, 1994.
2. Grandi, M., Pezzoni, G., Ballinari, D., Capolongo, L., Suarato, A., Bargiotti, A., Faiardi, D., and Spreafico, F. Novel anthracycline analogs. Cancer Treat. Rev., 17: 133-138, 1990.
3. Ripamonti, M., Pezzoni, G., Pesenti, E., Pastori, A., Farao, M., Bargiotti, A., Suarato, A., Spreafico, F., and Grandi, M. In vivo anti-tumour activity of FCE 23762, a methoxymorpholinyl derivative of doxorubicin active on doxorubicin-resistant tumour cells. Br. J. Cancer, 65: 703-707, 1992.
4. Danesi, R., Agen, C., Grandi, M., Nardini, V., Bevilacqua, G., and Del Tacca, M. 3′-Deamino-3′-(2-methoxy-4-morpholinyl)-doxombicin (FCE 23762): a new anthracycline derivative with enhanced cytotoxicity and reduced cardiotoxicity. Eur. J. Cancer, 11: 1560-1565, 1993.
5. Vasey, P. A., Bissett, D., Strolin-Benedetti, M., Poggesi, I., Breda, M., Adams, L., Wilson, P., Pacciarini, M. A., Kaye, S. B., and Cassidy, J. Phase 1 clinical and pharmacokinetic study of 3′-deamino-3′-(2-methoxy-4-morpholinyl)doxorubicin (FCE 23762). Cancer Res., 55: 2090-2096, 1995.
6. Ghielmini, M., Colli, E., Bosshard, G., Pennella, G., Geroni, C., Torri, V., D'Incalci, M., Cavalli, F., and Sessa, C. Hematotoxicity on human bone marrow- and umbilical cord blood-derived progenitor cells and in vitro therapeutic index of methoxymorpholinyldoxorubicin and its metabolites. Cancer Chemother. Pharmacol., 42: 235-240, 1998.
7. Quintieri, L., Rosato, A., Amboldi, N., Vizier, C., Ballinari, D., Zanovello, P., and Collavo, D. Delivery of methoxymorpholinyl doxorubicin by interleukin 2-activated NK cells: effect in mice bearing hepatic metastases. Br. J. Cancer, 79: 1067-1073, 1999.
8. Geroni, C., Pesenti, E., Broggini, M., Belvedere, G., Tagliabue, G., D'Incalci, M., Pennella, G., and Grandi, M. L1210 cells selected for resistance to methoxymorpholinyl doxorubicin appear specifically resistant to this class of morpholinyl derivatives. Br. J. Cancer, 69: 315-319, 1994.
9. Lau, D. H. M., Duran, G. E., and Sikic, B. I. The cellular and biochemical pharmacology of the methoxymorpholino derivative of doxorubicin, FCE 23762. Proc. Am. Assoc. Cancer Res., 32: 332, 1991.
10. Lau, D. H., Duran, G. E., Lewis, A. D., and Sikic, B. I. Metabolic conversion of methoxymorpholinyl doxorubicin: from a DNA strand breaker to a DNA cross-linker. Br. J. Cancer, 70: 79-84, 1994.
11. Lewis, A. D., Lau, D. H., Duran, G. E., Wolf, C. R., and Sikic, B. I. Role of cytochrome P-450 from the human CYP3A gene family in the potentiation of morpholino doxorubicin by human liver microsomes. Cancer Res., 52: 4379-4384, 1992.
12. Graham, M. A., Clugson, C. K., King, L. H., Riley, R. J., Morrison, C. G., Cummings, J., Kerr, D. J., and Workman, P. Mechanistic studies with methoxy-morpholino-doxorubicin: evidence of a novel covalent bound DNA adduct following activation by CYT P450 3A. Proc. Am. Assoc. Cancer Res., 33: 513, 1992.
13. Geroni, C., Caruso, M., Marsiglio, M., Lovisolo, P. P., Pennella, G., Mancini, L., and Grandi, M. Methoxymorpholinyldx (FCE 23762, PNU 152243) Isolation, structure identification, and biological characterization of active metabolites. Proc. Am. Assoc. Cancer Res., 38: 234, 1997.
14. Nelson, D. R., Koymans, L., Kamataki, T., Stegeman, J. J., Feyereisen, R., Waxman, D. J., Waterman, M. R., Gotoh, O., Coon, M. J., Estabrook, R. W., Gunsalus, I. C., and Nebert, D. W. P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature. Pharmacogenetics, 6: 1-42, 1996.
15. de Waziers, I., Cugnenc, P. H., Yang, C. S., Leroux, J. P., and Beaune, P. H. Cytochrome P 450 isoenzymes, epoxide hydrolase and glutathione transferases in rat and human hepatic and extrahepatic tissues. J. Pharmacol. Exp. Ther., 253: 387-394, 1990.
16. Wrighton, S. A., Schuetz, E. G., Watkins, P. B., Maurel, P., Barwick, J., Bailey, B. S., Hartle, H. T., Young, B., and Guzelian, P. Demonstration in multiple species of inducible hepatic cytochromes P-450 and their mRNAs related to the glucocorticoid-inducible cytochrome P-450 of the rat. Mol. Pharmacol., 28: 312-321, 1985.
17. Shimada, T., Yamazaki, H., Mimura, M., Inui, Y., and Guengerich, F. P. Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians. J. Pharmacol. Exp. Ther., 270: 414-423, 1994.
18. Kivisto, K. T., Kroemer, H. K., and Eichelbaum, M. The role of human cytochrome P450 enzymes in the metabolism of anticancer agents: implications for drug interactions. Br. J. Clin. Pharmacol., 40: 523-530, 1995.
19. Chang, T. K., Weber, G. F., Crespi, C. L., and Waxman, D. J. Differential activation of cyclophosphamide and ifosphamide by cytochromes P-450 2B and 3A in human liver microsomes. Cancer Res., 53: 5629-5637, 1993.
20. Murray, G. I., Paterson, P. J., Weaver, R. J., Ewen, S. W., Melvin, W. T., and Burke, M. D. The expression of cytochrome P-450, epoxide hydrolase, and glutathione S-transferase in hepatocellular carcinoma. Cancer (Phila.), 71: 36-43, 1993.
21. Murray, G. I., McKay, J. A., Weaver, R. J., Ewen, S. W., Melvin, W. T., and Burke, M. D. Cytochrome P450 expression is a common molecular event in soft tissue sarcomas. J. Pathol., 171: 49-52, 1993.
22. Murray, G. I., Taylor, V. E., McKay, J. A., Weaver, R. J., Ewen, S. W., Melvin, W. T., and Burke, M. D. The immunohistochemical localization of drug-metabolizing enzymes in prostate cancer. J. Pathol., 177: 147-152, 1995.
23. de Waziers, I., Cugnenc, P. H., Berger, A., Leroux, J. P., and Beaune, P. H. Drug-metabolizing enzyme expression in human normal, peritumoral and tumoral colorectal tissue samples. Carcinogenesis (Lond.), 12: 905-909, 1991.
24. Waxman, D. J. P450 gene induction by structurally diverse xenochemicals: central role of nuclear receptors CAR, PXR, and PPAR. Arch. Biochem. Biophys., 369: 11-23, 1999.
25. Thummel, K. E., and Wilkinson, G. R. In vitro and in vivo drug interactions involving human CYP3A. Annu. Rev. Pharmacol. Toxicol., 38: 389-430, 1998.
26. Floreani, M., and Carpenedo, F. Inhibition of rat liver monooxygenase activities by 2-methyl-1,4-naphthoquinone (menadione). Toxicol. Appl. Pharmacol., 105: 333-339, 1990.
27. Omura, T., and Sato, R. The carbon monoxide-binding pigment of liver microsomes. II. Solubilization, purification, and properties. J. Biol. Chem., 239: 2379-2385, 1964.
28. Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J. Protein measurement with the Folin-phenol reagent. J. Biol. Chem., 193: 265-275, 1951.
29. Burke, M. D., Thompson, S., Elcombe, C. R., Halpert, J., Haaparanta, T., and Mayer, R. T. Ethoxy-, pentoxy- and benzyloxyphenoxazones and homologues: a series of substrates to distinguish between different induced cytochromes P-450. Biochem. Pharmacol., 34: 3337-3345, 1985.
30. Nash, T. The colorimetric estimation of formaldehyde by means of the Hantzsch reaction. Biochem. J., 55: 416-422, 1953.
31. McLean, A. E., and Day, P. A. The use of new methods to measure: the effect of diet and inducers of microsomal enzyme synthesis on cytochrome P-450 in liver homogenates, and on metabolism of dimethyl nitrosamine. Biochem. Pharmacol., 23: 1173-1180, 1974.
32. Chang, T. K., Gonzalez, F. J., and Waxman, D. J. Evaluation of triacetyloleandomycin, α-naphthoflavone and diethyldithiocarbamate as selective chemical probes for inhibition of human cytochromes P450. Arch. Biochem. Biophys., 311: 437-442, 1994.
33. Ono, S., Hatanaka, T., Hotta, H., Satoh, T., Gonzalez, F. J., and Tsutsui, M. Specificity of substrate and inhibitor probes for cytochrome P450s: evaluation of in vitro metabolism using cDNA-expressed human P450s and human liver microsomes. Xenobiotica, 26: 681-693, 1996.
34. Mosmann, T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods, 65: 55-63, 1983.
35. Nerurkar, P. V., Park, S. S., Thomas, P. E., Nims, R. W., and Lubet, R. A. Methoxyresorufin and benzyloxyresorufin: substrates preferentially metabolized by cytochromes P4501A2 and 2B, respectively, in the rat and mouse. Biochem. Pharmacol., 46: 933-943, 1993.
36. Pessayre, D., Larrey, D., Vitaux, J., Breil, P., Belghiti, J., and Benhamou, J. P. Formation of an inactive cytochrome P-450 Fe(II)-metabolite complex after administration of troleandomycin in humans. Biochem. Pharmacol., 31: 1699-1704, 1982.
37. Larrey, D., Tinel, M., and Pessayre, D. Formation of inactive cytochrome P-450 Fe(II)-metabolite complexes with several erythromycin derivatives but not with josamycin and midecamycin in rats. Biochem. Pharmacol., 32: 1487-1493, 1983.
38. Hart, I. R., Talmadge, J. E., and Fidler, I. J. Metastatic behavior of a murine reticulum cell sarcoma exhibiting organ-specific growth. Cancer Res., 41: 1281-1287, 1981.
39. Ndikum-Moffor, F. M., Schoeb, T. R., and Roberts, S. M. Liver toxicity from norcocaine nitroxide, an N-oxidative metabolite of cocaine. J. Pharmacol. Exp. Ther., 284: 413-419, 1998.
40. Pellinen, P., Honkakoski, P., Stenback, F., Niemitz, M., Alhava, E., Pelkonen, O., Lang, M. A., and Pasanen, M. Cocaine N-demethylation and the metabolism-related hepatotoxicity can be prevented by cytochrome P450 3A inhibitors. Eur. J. Pharmacol., 270: 35-43, 1994.
41. Acton, E. M., Tong, G. L., Mosher, C. W., and Wolgemuth, R. L. Intensely potent morpholinyl anthracyclines. J. Med. Chem., 27: 638-645, 1984.
42. Yu, L. J., Drewes, P., Gustafsson, K., Brain, E. G., Hecht, J. E., and Waxman, D. J. In vivo modulation of alternative pathways of P-450-catalyzed cyclophosphamide metabolism: impact on pharmacokinetics and antitumor activity. J. Pharmacol. Exp. Ther., 288: 928-937, 1999.
43. Kostrubsky, V. E., Szakacs, J. G., Jeffery, E. H., Wood, S. G., Bement, W. J., Wrighton, S. A., Sinclair, P. R., and Sinclair, J. F. Role of CYP3A in ethanol-mediated increases in acetaminophen hepatotoxicity. Toxicol. Appl. Pharmacol., 143: 315-323, 1997.
44. Kharasch, E. D., Russell, M., Mautz, D., Thummel, K. E., Kunze, K. L., Bowdle, A., and Cox, K. The role of cytochrome P450 3A4 in alfentanil clearance. Implications for interindividual variability in disposition and perioperative drug interactions. Anesthesiology, 87: 36-50, 1997.
45. Alley, M. C., Powis, G., Appel, P. L., Kooistra, K. L., and Lieber, M. M. Activation and inactivation of cancer chemotherapeutic agents by rat hepatocytes cocultured with human tumor cell lines. Cancer Res., 44: 549-556, 1984.
46. Sladek, N. E. Therapeutic efficacy of cyclophosphamide as a function of its metabolism. Cancer Res., 32: 535-542, 1972.
47. Farber, E. Cellular biochemistry of the stepwise development of cancer with chemicals: G. H. A. Clowes memorial lecture. Cancer Res., 44: 5463-5374, 1984.
48. Chen, L., Waxman, D. J., Chen, D., and Kufe, D. W. Sensitization of human breast cancer cells to cyclophosphamide and ifosfamide by transfer of a liver cytochrome P450 gene. Cancer Res., 56: 1331-1340, 1996.