The dual-targeted HER1/HER2 tyrosine kinase inhibitor lapatinib strongly potentiates the cardiac myocyte-damaging effects of doxorubicin

Cardiovascular Toxicology

Volumn 13, Issue 1, 2013, Pages 33-47

  Hasinoff, Brian B ^a   Patel, Daywin ^a   Wu, Xing ^a  

^a UNIVERSITY OF MANITOBA   (Canada)

Author keywords

Cardiac myocytes; Cardiotoxicity; Doxorubicin; Efflux; Flow cytometry; HER2; Lapatinib; Tyrosine kinase inhibitor

Indexed keywords

ADENOSINE TRIPHOSPHATE; CASPASE 3; CASPASE 7; DOXORUBICIN; LACTATE DEHYDROGENASE; LAPATINIB; MITOGEN ACTIVATED PROTEIN KINASE; RAZOXANE;

ANIMAL CELL; ANIMAL CELL CULTURE; ARTICLE; CELL DAMAGE; CELL ISOLATION; CELL PROTECTION; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG MECHANISM; DRUG POTENTIATION; DRUG TRANSPORT; ENZYME PHOSPHORYLATION; EPIFLUORESCENCE MICROSCOPY; FLOW CYTOMETRY; HEART MUSCLE CELL; NEWBORN; NONHUMAN; OXIDATIVE STRESS; PHARMACOLOGICAL BLOCKING; PRIORITY JOURNAL; PROTEIN ISOLATION; RAT; WESTERN BLOTTING;

ANIMALS; ANIMALS, NEWBORN; CELLS, CULTURED; DOSE-RESPONSE RELATIONSHIP, DRUG; DOXORUBICIN; DRUG DELIVERY SYSTEMS; DRUG SYNERGISM; MYOCYTES, CARDIAC; PROTEIN KINASE INHIBITORS; PROTEIN-TYROSINE KINASES; QUINAZOLINES; RATS; RATS, SPRAGUE-DAWLEY; RECEPTOR, EPIDERMAL GROWTH FACTOR; RECEPTOR, ERBB-2;

RATTUS;

EID: 84872558572     PISSN: 15307905     EISSN: 15590259     Source Type: Journal    
DOI: 10.1007/s12012-012-9183-x     Document Type: Article

References (58)

1. Slamon, D. J.; Leyland-Jones, B.; Shak, S.; Fuchs, H.; Paton, V.; Bajamonde, A.; et al. (2001). Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. New England Journal of Medicine, 344, 783-792. (Pubitemid 32222155)
2. Gewirtz, D. A. (1999). A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin. Biochemical Pharmacology, 57, 727-741. (Pubitemid 29094544)
3. Gennari, A.; & Pronzato, P. (2008). New understanding of the role of anthracyclines in early-stage breast cancer: Patient selection considerations. Clinical Breast Cancer, 8(Suppl 4), S179-S183.
4. Di Leo, A.; Biganzoli, L.; Claudino, W.; Licitra, S.; Pestrin, M.; & Larsimont, D. (2008). Topoisomerase II alpha as a marker predicting anthracyclines' activity in early breast cancer patients: Ready for the primetime? European Journal of Cancer, 44, 2791-2798.
5. Jarvinen, T. A.; Tanner, M.; Rantanen, V.; Barlund, M.; Borg, A.; Grenman, S.; et al. (2000). Amplification and deletion of topoisomerase IIα associate with ErbB-2 amplification and affect sensitivity to topoisomerase II inhibitor doxorubicin in breast cancer. American Journal of Pathology, 156, 839-847. (Pubitemid 30626942)
6. Pal, S. K.; Childs, B. H.; & Pegram, M. (2010). Emergence of nonanthracycline regimens in the adjuvant treatment of breast cancer. Breast Cancer Research and Treatment, 119, 25-32.
7. Fortune, J. M.; & Osheroff, N. (2000). Topoisomerase II as a target for anticancer drugs: When enzymes stop being nice. Progress in Nucleic Acid Research and Molecular Biology, 64, 221-253.
8. Cheng, H.; & Force, T. (2010). Molecular mechanisms of cardiovascular toxicity of targeted cancer therapeutics. Circulation Research, 106, 21-34.
9. Perez, E. A.; Koehler, M.; Byrne, J.; Preston, A. J.; Rappold, E.; & Ewer, M. S. (2008). Cardiac safety of lapatinib: Pooled analysis of 3689 patients enrolled in clinical trials. Mayo Clinic Proceedings, 83, 679-686. (Pubitemid 351810568)
10. Dang, C.; Lin, N.; Moy, B.; Come, S.; Sugarman, S.; Morris, P.; et al. (2010). Dose-dense doxorubicin and cyclophosphamide followed by weekly paclitaxel with trastuzumab and lapatinib in HER2/neu-overexpressed/amplified breast cancer is not feasible because of excessive diarrhea. Journal of Clinical Oncology, 28, 2982-2988.
11. Wonders, K. Y.; Hydock, D. S.; Greufe, S.; Schneider, C. M.; & Hayward, R. (2009). Endurance exercise training preserves cardiac function in rats receiving doxorubicin and the HER-2 inhibitor GW2974. Cancer Chemotherapy and Pharmacology, 64, 1105-1113.
12. Goukassian, D.; Sasi, S.; Lee, J.; Budiu, D.; Lawson, C.; Maysky, et al. (2011). Concurrent administration of doxorubicin and lapatinib worsens doxorubicin-induced cardiac dysfunction in mice. In Proceedings of the American Association for Cancer Research, Abstract number 1209.
13. Fedele, C.; Riccio, G.; Coppola, C.; Barbieri, A.; Monti, M. G.; Arra, C.; et al. (2012). Comparison of preclinical cardiotoxic effects of different ErbB2 inhibitors. Breast Cancer Research and Treatment, 133, 511-521.
14. Karaman, M. W.; Herrgard, S.; Treiber, D. K.; Gallant, P.; Atteridge, C. E.; Campbell, B. T.; et al. (2008). A quantitative analysis of kinase inhibitor selectivity. Nature Biotechnology, 26, 127-132.
15. Wiig, H.; Gyenge, C. C.; & Tenstad, O. (2005). The interstitial distribution of macromolecules in rat tumours is influenced by the negatively charged matrix components. Journal of Physiology, 567, 557-567. (Pubitemid 41301051)
16. Brozik, A.; Hegedus, C.; Erdei, Z.; Hegedus, T.; Ozvegy-Laczka, C.; Szakacs, G.; et al. (2011). Tyrosine kinase inhibitors as modulators of ATP binding cassette multidrug transporters: substrates, chemosensitizers or inducers of acquired multidrug resistance? Expert Opinion on Drug Metabolism and Toxicology, 7, 623-642.
17. Kuang, Y. H.; Shen, T.; Chen, X.; Sodani, K.; Hopper-Borge, E.; Tiwari, A. K.; et al. (2010). Lapatinib and erlotinib are potent reversal agents for MRP7 (ABCC10)-mediated multidrug resistance. Biochemical Pharmacology, 79, 154-161.
18. Hegedus, C.; Szakacs, G.; Homolya, L.; Orban, T. I.; Telbisz, A.; Jani, M.; et al. (2009). Ins and outs of the ABCG2 multidrug transporter: an update on in vitro functional assays. Advanced Drug Delivery Reviews, 61, 47-56.
19. Hasinoff, B. B.; & Patel, D. (2010). The lack of target specificity of small molecule anticancer kinase inhibitors is correlated with their ability to damage myocytes in vitro. Toxicology and Applied Pharmacology, 249, 132-139.
20. Hasinoff, B. B. (2010). The cardiotoxicity and myocyte damage caused by small molecule anticancer tyrosine kinase inhibitors is correlated with lack of target specificity. Toxicology and Applied Pharmacology, 244, 190-195.
21. Burris, H. A.; 3rd, Taylor, C. W.; Jones, S. F.; Koch, K. M.; Versola, M. J.; Arya, N.; et al. (2009). A phase I and pharmacokinetic study of oral lapatinib administered once or twice daily in patients with solid malignancies. Clinical Cancer Research, 15, 6702-6708.
22. Schroeder, P. E.; Patel, D.; & Hasinoff, B. B. (2008). The dihydroorotase inhibitor 5-aminoorotic acid inhibits the metabolism in the rat of the cardioprotective drug dexrazoxane and its one-ring open metabolites. Drug Metabolism and Disposition, 36, 1780-1785.
23. Hasinoff, B. B.; Patel, D.; & Wu, X. (2007). The cytotoxicity of celecoxib towards cardiac myocytes is cyclooxygenase-2 independent. Cardiovascular Toxicology, 7, 19-27. (Pubitemid 47338488)
24. Hasinoff, B. B.; Patel, D.; & O'Hara, K. A. (2008). Mechanisms of myocyte cytotoxicity induced by the multiple receptor tyrosine kinase inhibitor sunitinib. Molecular Pharmacology, 74, 1722-1728.
25. Hasinoff, B. B.; & Patel, D. (2010). Mechanisms of myocyte cytotoxicity induced by the multikinase inhibitor sorafenib. Cardiovascular Toxicology, 10, 1-8.
26. Reers, M.; Smiley, S. T.; Mottola-Hartshorn, C.; Chen, A.; Lin, M.; & Chen, L. B. (1995). Mitochondrial membrane potential monitored by JC-1 dye. Methods in Enzymology, 260, 406-417.
27. Hasinoff, B. B.; Schnabl, K. L.; Marusak, R. A.; Patel, D.; & Huebner, E. (2003). Dexrazoxane (ICRF-187) protects cardiac myocytes against doxorubicin by preventing damage to mitochondria. Cardiovascular Toxicology, 3, 89-99. (Pubitemid 41490357)
28. Adderley, S. R.; & Fitzgerald, D. J. (1999). Oxidative damage of cardiomyocytes is limited by extracellular regulated kinases 1/2-mediated induction of cyclooxygenase-2. Journal of Biological Chemistry, 274, 5038-5046.
29. Li, F.; Wang, X.; Capasso, J. M.; & Gerdes, A. M. (1996). Rapid transition of cardiac myocytes from hyperplasia to hypertrophy during postnatal development. Journal of Molecular and Cellular Cardiology, 28, 1737-1746. (Pubitemid 26300573)
30. Hasinoff, B. B.; & Patel, D. (2009). The iron chelator Dp44mT does not protect myocytes against doxorubicin. Journal of Inorganic Biochemistry, 103, 1093-1101.
31. Hochster, H.; Liebes, L.; Wadler, S.; Oratz, R.; Wernz, J. C.; Meyers, M.; et al. (1992). Pharmacokinetics of the cardioprotector ADR-529 (ICRF-187) in escalating doses combined with fixed-dose doxorubicin. Journal of the National Cancer Institute, 84, 1725-1730.
32. Hasinoff, B. B.; Patel, D.; & Wu, X. (2003). The oral iron chelator ICL670A (deferasirox) does not protect myocytes against doxorubicin. Free Radical Biology & Medicine, 35, 1469-1479. (Pubitemid 37452472)
33. Hasinoff, B. B.; & Herman, E. H. (2007). Dexrazoxane: How it works in cardiac and tumor cells. Is it a prodrug or is it a drug? Cardiovascular Toxicology, 7, 140-144. (Pubitemid 47339861)
34. Wang, G. Q.; Gong, Y.; Burczynski, F. J.; & Hasinoff, B. B. (2008). Cell lysis with dimethyl sulfoxide produces stable homogeneous solutions in the dichlorofluorescin oxidative stress assay. Free Radical Research, 42, 435-441. (Pubitemid 351935157)
35. Carloni, S.; Fabbri, F.; Brigliadori, G.; Ulivi, P.; Silvestrini, R.; Amadori, D.; et al. (2010). Tyrosine kinase inhibitors gefitinib, lapatinib and sorafenib induce rapid functional alterations in breast cancer cells. Current Cancer Drug Targets, 10, 422-431.
36. Spector, N. L.; Yarden, Y.; Smith, B.; Lyass, L.; Trusk, P.; Pry, K.; et al. (2007). Activation of AMP-activated protein kinase by human EGF receptor 2/EGF receptor tyrosine kinase inhibitor protects cardiac cells. Proceedings of the National Academy of Sciences of the United States of America, 104, 10607-10612. (Pubitemid 47185712)
37. Shell, S. A.; Lyass, L.; Trusk, P. B.; Pry, K. J.; Wappel, R. L.; & Bacus, S. S. (2008). Activation of AMPK is necessary for killing cancer cells and sparing cardiac cells. Cell Cycle, 7, 1769-1775. (Pubitemid 351988742)
38. Force, T.; & Kolaja, K. L. (2011). Cardiotoxicity of kinase inhibitors: the prediction and translation of preclinical models to clinical outcomes. Nature Reviews Drug Discovery, 10, 111-126.
39. Force, T.; Krause, D. S.; & Van Etten, R. A. (2007). Molecular mechanisms of cardiotoxicity of tyrosine kinase inhibition. Nature Reviews Cancer, 7, 332-344. (Pubitemid 46652481)
40. Wilhelm, S. M.; Carter, C.; Tang, L.; Wilkie, D.; McNabola, A.; Rong, H.; et al. (2004). BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Research, 64, 7099-7109. (Pubitemid 39331023)
41. Xia, W.; Husain, I.; Liu, L.; Bacus, S.; Saini, S.; Spohn, J.; et al. (2007). Lapatinib antitumor activity is not dependent upon phosphatase and tensin homologue deleted on chromosome 10 in ErbB2-overexpressing breast cancers. Cancer Research, 67, 1170-1175.
42. Lemmens, K.; Doggen, K.; & De Keulenaer, G. W. (2011). Activation of the neuregulin/ErbB system during physiological ventricular remodeling in pregnancy. American Journal of Physiology Heart and Circulatory Physiology, 300, H931-H942.
43. Polli, J. W.; Olson, K. L.; Chism, J. P.; John-Williams, L. S.; Yeager, R. L.; Woodard, S. M.; et al. (2009). An unexpected synergist role of P-glycoprotein and breast cancer resistance protein on the central nervous system penetration of the tyrosine kinase inhibitor lapatinib (N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methylsulfonyl)ethy l]amino}methyl)-2-furyl]-4-quinazolinamine; GW572016). Drug Metabolism and Disposition, 37, 439-442.
44. Polli, J. W.; Humphreys, J. E.; Harmon, K. A.; Castellino, S.; O'Mara, M. J.; Olson, K. L.; et al. (2008). The role of efflux and uptake transporters in [N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methylsulfonyl)ethy l]amino}methyl)-2-furyl]-4-quinazolinamine (GW572016, lapatinib) disposition and drug interactions. Drug Metabolism and Disposition, 36, 695-701. (Pubitemid 351468376)
45. Dai, C. L.; Tiwari, A. K.; Wu, C. P.; Su, X. D.; Wang, S. R.; Liu, D. G.; et al. (2008). Lapatinib (Tykerb, GW572016) reverses multidrug resistance in cancer cells by inhibiting the activity of ATP-binding cassette subfamily B member 1 and G member 2. Cancer Research, 68, 7905-7914.
46. Akimoto, H.; Bruno, N. A.; Slate, D. L.; Billingham, M. E.; Torti, S. V.; & Torti, F. M. (1993). Effect of verapamil on doxorubicin cardiotoxicity: altered muscle gene expression in cultured neonatal rat cardiomyocytes. Cancer Research, 53, 4658-4664. (Pubitemid 23304396)
47. Kwatra, D.; Vadlapatla, R. K.; Vadlapudi, A. D.; Pal, D.; & Mitra, A. K. (2010). Interaction of gatifloxacin with efflux transporters: a possible mechanism for drug resistance. International Journal of Pharmaceutics, 395, 114-121.
48. Weiss, J.; Dormann, S. M.; Martin-Facklam, M.; Kerpen, C. J.; Ketabi-Kiyanvash, N.; & Haefeli, W. E. (2003). Inhibition of P-glycoprotein by newer antidepressants. Journal of Pharmacology and Experimental Therapeutics, 305, 197-204. (Pubitemid 36373851)
49. Crone, S. A.; Zhao, Y. Y.; Fan, L.; Gu, Y.; Minamisawa, S.; Liu, Y.; et al. (2002). ErbB2 is essential in the prevention of dilated cardiomyopathy. Nature Medicine, 8, 459-465. (Pubitemid 34546747)
50. Pentassuglia, L.; Graf, M.; Lane, H.; Kuramochi, Y.; Cote, G.; Timolati, F.; et al. (2009). Inhibition of ErbB2 by receptor tyrosine kinase inhibitors causes myofibrillar structural damage without cell death in adult rat cardiomyocytes. Experimental Cell Research, 315, 1302-1312.
51. Cvetkovic, R. S.; & Scott, L. J. (2005). Dexrazoxane: a review of its use for cardioprotection during anthracycline chemotherapy. Drugs, 65, 1005-1024. (Pubitemid 40667518)
52. Miyamoto, S.; Murphy, A. N.; & Brown, J. H. (2009). Akt mediated mitochondrial protection in the heart: metabolic and survival pathways to the rescue. Journal of Bioenergetics and Biomembranes, 41, 169-180.
53. Kim, S. Y.; Kim, H. P.; Kim, Y. J.; Oh do, Y.; Im, S. A.; et al. (2008). Trastuzumab inhibits the growth of human gastric cancer cell lines with HER2 amplification synergistically with cisplatin. International Journal of Oncology, 32, 89-95. (Pubitemid 351176065)
54. Giacomini, K. M.; Huang, S. M.; Tweedie, D. J.; Benet, L. Z.; Brouwer, K. L.; Chu, X.; et al. (2010). Membrane transporters in drug development. Nature Reviews Drug Discovery, 9, 215-236.
55. Vannini, I.; Zoli, W.; Fabbri, F.; Ulivi, P.; Tesei, A.; Carloni, S.; et al. (2009). Role of efflux pump activity in lapatinib/caelyx combination in breast cancer cell lines. Anti-Cancer Drugs, 20, 918-925.
56. Estevez, M. D.; Wolf, A.; & Schramm, U. (2000). Effect of PSC 833, verapamil and amiodarone on adriamycin toxicity in cultured rat cardiomyocytes. Toxicology in Vitro, 14, 17-23. (Pubitemid 30122810)
57. McBride, B. F.; Yang, T.; Liu, K.; Urban, T. J.; Giacomini, K. M.; Kim, R. B.; et al. (2009). The organic cation transporter, OCTN1, expressed in the human heart, potentiates antagonism of the HERG potassium channel. Journal of Cardiovascular Pharmacology, 54, 63-71.
58. Solbach, T. F.; Paulus, B.; Weyand, M.; Eschenhagen, T.; Zolk, O.; & Fromm, M. F. (2008). ATP-binding cassette transporters in human heart failure. Naunyn-Schmiedeberg's Archives of Pharmacology, 377, 231-243.