Detection of statin cytotoxicity is increased in cells expressing the OATP1B1 transporter

Toxicological Sciences

Volumn 134, Issue 1, 2013, Pages 73-82

  Zhang, Xun ^a   Scialis, Renato J ^a   Feng, Bo ^a   Leach, Karen ^a  

^a PFIZER INC   (United States)

Author keywords

Cytotoxicity; OATP1B1; Permeability; Statin; Uptake transporter

Indexed keywords

CERIVASTATIN; FLUINDOSTATIN; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; ORGANIC ANION TRANSPORTER; PITAVASTATIN; PRAVASTATIN; PROTEIN OATP1B1; RIFAMPICIN; ROSUVASTATIN; UNCLASSIFIED DRUG; SLCO1B1 PROTEIN, HUMAN;

ARTICLE; CELL LEVEL; CELL MEMBRANE PERMEABILITY; CELL STRAIN HEK293; CELL STRAIN HEPG2; CELL VIABILITY; CONTROLLED STUDY; DRUG CYTOTOXICITY; DRUG PENETRATION; DRUG POTENCY; DRUG SCREENING; DRUG SENSITIVITY; DRUG UPTAKE; GENE EXPRESSION; HUMAN; HUMAN CELL; IC 50; MOLECULAR MODEL; REAL TIME POLYMERASE CHAIN REACTION; WILD TYPE; ANTAGONISTS AND INHIBITORS; CELL SURVIVAL; CHEMISTRY; CULTURE TECHNIQUE; DOSE RESPONSE; DRUG EFFECTS; ENZYME SPECIFICITY; GENETIC TRANSFECTION; GENETICS; HEK293 CELL LINE; HEPG2 CELL LINE; IC50; LIVER CELL; METABOLISM; TOXICITY;

CELL CULTURE TECHNIQUES; CELL SURVIVAL; DOSE-RESPONSE RELATIONSHIP, DRUG; HEK293 CELLS; HEP G2 CELLS; HEPATOCYTES; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; INHIBITORY CONCENTRATION 50; ORGANIC ANION TRANSPORTERS; REAL-TIME POLYMERASE CHAIN REACTION; RIFAMPIN; SUBSTRATE SPECIFICITY; TRANSFECTION;

EID: 84880849536     PISSN: 10966080     EISSN: 10960929     Source Type: Journal    
DOI: 10.1093/toxsci/kft085     Document Type: Article

References (47)

1. Arrowsmith, J. (2011a). Trial watch: Phase II failures: 2008-2010. Nat. Rev. Drug Discov. 10, 328-329.
2. Arrowsmith, J. (2011b). Trial watch: Phase III and submission failures: 2007-2010. Nat. Rev. Drug Discov. 10, 87.
3. Cihlar, T., Lin, D. C., Pritchard, J. B., Fuller, M. D., Mendel, D. B., and Sweet, D. H. (1999). The antiviral nucleotide analogs cidofovir and adefovir are novel substrates for human and rat renal organic anion transporter 1. Mol. Pharmacol. 56, 570-580.
4. Cole, S. P., and Deeley, R. G. (1998). Multidrug resistance mediated by the ATP-binding cassette transporter protein MRP. Bioessays 20, 931-940.
5. Decorti, G., Peloso, I., Favarin, D., Klugmann, F. B., Candussio, L., Crivellato, E., Mallardi, F., and Baldini, L. (1998). Handling of doxorubicin by the LLC-PK1 kidney epithelial cell line. J. Pharmacol. Exp. Ther. 286, 525-530.
6. Doyle, L. A., Yang, W., Abruzzo, L. V., Krogmann, T., Gao, Y., Rishi, A. K., and Ross, D. D. (1998). A multidrug resistance transporter from human MCF-7 breast cancer cells. Proc. Natl. Acad. Sci. U. S. A. 95, 15665-15670.
7. Evers, R., and Chu, X. Y. (2008). Role of the murine organic anion-transporting polypeptide 1b2 (Oatp1b2) in drug disposition and hepatotoxicity. Mol. Pharmacol. 74, 309-311.
8. Fischer, A., Hoeger, S. J., Stemmer, K., Feurstein, D. J., Knobeloch, D., Nussler, A., and Dietrich, D. R. (2010). The role of organic anion transporting polypeptides (OATPs/SLCOs) in the toxicity of different microcystin congeners in vitro: A comparison of primary human hepatocytes and OATP-transfected HEK293 cells. Toxicol. Appl. Pharmacol. 245, 9-20.
9. Giacomini, K. M., Huang, S. M., Tweedie, D. J., Benet, L. Z., Brouwer, K. L., Chu, X., Dahlin, A., Evers, R., Fischer, V., Hillgren, K. M., et al. (2010). Membrane transporters in drug development. Nat. Rev. Drug Discov. 9, 215-236.
10. Gottesman, M. M., Fojo, T., and Bates, S. E. (2002). Multidrug resistance in cancer: Role of ATP-dependent transporters. Nat. Rev. Cancer 2, 48-58.
11. Greene, N., Aleo, M. D., Louise-May, S., Price, D. A., and Will, Y. (2010). Using an in vitro cytotoxicity assay to aid in compound selection for in vivo safety studies. Bioorg. Med. Chem. Lett. 20, 5308-5312.
12. Greene, N., and Song, M. (2011). Predicting in vivo safety characteristics using physiochemical properties and in vitro assays. Future Med. Chem. 3, 1503-1511.
13. Gupta, N., Pant, S. C., Vijayaraghavan, R., and Rao, P. V. (2003). Comparative toxicity evaluation of cyanobacterial cyclic peptide toxin microcystin variants (LR, RR, YR) in mice. Toxicology 188, 285-296.
14. Hagenbuch, B., and Gui, C. (2008). Xenobiotic transporters of the human organic anion transporting polypeptides (OATP) family. Xenobiotica. 38, 778-801.
15. Hamelin, B. A., and Turgeon, J. (1998). Hydrophilicity/lipophilicity: Relevance for the pharmacology and clinical effects of HMG-CoA reductase inhibitors. Trends Pharmacol. Sci. 19, 26-37.
16. Hilgendorf, C., Ahlin, G., Seithel, A., Artursson, P., Ungell, A. L., and Karlsson, J. (2007). Expression of thirty-six drug transporter genes in human intestine, liver, kidney, and organotypic cell lines. Drug Metab. Dispos. 35, 1333-1340.
17. Hirano, M., Maeda, K., Shitara, Y., and Sugiyama, Y. (2004). Contribution of OATP2 (OATP1B1) and OATP8 (OATP1B3) to the hepatic uptake of pitavastatin in humans. J. Pharmacol. Exp. Ther. 311, 139-146.
18. Ho, E. S., Lin, D. C., Mendel, D. B., and Cihlar, T. (2000). Cytotoxicity of antiviral nucleotides adefovir and cidofovir is induced by the expression of human renal organic anion transporter 1. J. Am. Soc. Nephrol. 11, 383-393.
19. Hsiang, B., Zhu, Y., Wang, Z., Wu, Y., Sasseville, V., Yang, W. P., and Kirchgessner, T. G. (1999). A novel human hepatic organic anion transporting polypeptide (OATP2). Identification of a liver-specific human organic anion transporting polypeptide and identification of rat and human hydroxymethylglutaryl-CoA reductase inhibitor transporters. J. Biol. Chem. 274, 37161-37168.
20. Huang, S. M., and Woodcock, J. (2010). Transporters in drug development: Advancing on the Critical Path. Nat. Rev. Drug Discov. 9, 175-176.
21. Jochimsen, E. M., Carmichael, W. W., An, J. S., Cardo, D. M., Cookson, S. T., Holmes, C. E., Antunes, M. B., de Melo Filho, D. A., Lyra, T. M., Barreto, V. S., et al. (1998). Liver failure and death after exposure to microcystins at a hemodialysis center in Brazil. N. Engl. J. Med. 338, 873-878.
22. Kepp, O., Galluzzi, L., Lipinski, M., Yuan, J., and Kroemer, G. (2011). Cell death assays for drug discovery. Nat. Rev. Drug Discov. 10, 221-237. Krishnamurthy, P., Schwab, M., Takenaka, K., Nachagari, D., Morgan, J.,
23. Krishnamurthy, P., Schwab, M., Takenaka, K., Nachagari, D., Morgan, J., Leslie, M., Du, W., Boyd, K., Cheok, M., Nakauchi, H., et al. (2008). Transporter-mediated protection against thiopurine-induced hematopoietic toxicity. Cancer Res. 68, 4983-4989.
24. Libra, A., Fernetti, C., Lorusso, V., Visigalli, M., Anelli, P. L., Staud, F., Tiribelli, C., and Pascolo, L. (2006). Molecular determinants in the transport of a bile acid-derived diagnostic agent in tumoral and nontumoral cell lines of human liver. J. Pharmacol. Exp. Ther. 319, 809-817.
25. Link, E., Parish, S., Armitage, J., Bowman, L., Heath, S., Matsuda, F., Gut, I., Lathrop, M., Collins, R., and SEARCH Collaborative Group. (2008). SLCO1B1 variants and statin-induced myopathy-a genomewide study. N. Engl. J. Med. 359, 789-799.
26. Lu, H., Choudhuri, S., Ogura, K., Csanaky, I. L., Lei, X., Cheng, X., Song, P. Z., and Klaassen, C. D. (2008). Characterization of organic anion transporting polypeptide 1b2-null mice: Essential role in hepatic uptake/toxicity of phalloidin and microcystin-LR. Toxicol. Sci. 103, 35-45.
27. Mizuno, N., Niwa, T., Yotsumoto, Y., and Sugiyama, Y. (2003). Impact of drug transporter studies on drug discovery and development. Pharmacol. Rev. 55, 425-461.
28. Monks, N. R., Liu, S., Xu, Y., Yu, H., Bendelow, A. S., and Moscow, J. A. (2007). Potent cytotoxicity of the phosphatase inhibitor microcystin LR and microcystin analogues in OATP1B1-and OATP1B3-expressing HeLa cells. Mol. Cancer Ther. 6, 587-598.
29. Nezasa, K., Higaki, K., Takeuchi, M., Nakano, M., and Koike, M. (2003). Uptake of rosuvastatin by isolated rat hepatocytes: Comparison with pravastatin. Xenobiotica. 33, 379-388.
30. Niemi, M., Pasanen, M. K., and Neuvonen, P. J. (2011). Organic anion transporting polypeptide 1B1: A genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol. Rev. 63, 157-181.
31. Nishimura, M., and Naito, S. (2005). Tissue-specific mRNA expression profiles of human ATP-binding cassette and solute carrier transporter superfamilies. Drug Metab. Pharmacokinet. 20, 452-477.
32. Obaidat, A., Roth, M., and Hagenbuch, B. (2012). The expression and function of organic anion transporting polypeptides in normal tissues and in cancer. Annu. Rev. Pharmacol. Toxicol. 52, 135-151.
33. Oballa, R. M., Belair, L., Black, W. C., Bleasby, K., Chan, C. C., Desroches, C., Du, X., Gordon, R., Guay, J., Guiral, S., et al. (2011). Development of a liver-targeted stearoyl-CoA desaturase (SCD) inhibitor (MK-8245) to establish a therapeutic window for the treatment of diabetes and dyslipidemia. J. Med. Chem. 54, 5082-5096.
34. Pfefferkorn, J. A., Guzman-Perez, A., Litchfield, J., Aiello, R., Treadway, J. L., Pettersen, J., Minich, M. L., Filipski, K. J., Jones, C. S., Tu, M., et al. (2012). Discovery of (S)-6-(3-cyclopentyl-2-(4-(trifluoromethyl)-1H-imidazol-1-yl) propanamido)nicotinic acid as a hepatoselective glucokinase activator clinical candidate for treating type 2 diabetes mellitus. J. Med. Chem. 55, 1318-1333.
35. Riordan, J. R., Deuchars, K., Kartner, N., Alon, N., Trent, J., and Ling, V. (1985). Amplification of P-glycoprotein genes in multidrug-resistant mammalian cell lines. Nature 316, 817-819.
36. Sakamoto, K., Mikami, H., and Kimura, J. (2008). Involvement of organic anion transporting polypeptides in the toxicity of hydrophilic pravastatin and lipophilic fluvastatin in rat skeletal myofibres. Br. J. Pharmacol. 154, 1482-1490.
37. Sugano, K., Kansy, M., Artursson, P., Avdeef, A., Bendels, S., Di, L., Ecker, G. F., Faller, B., Fischer, H., Gerebtzoff, G., et al. (2010). Coexistence of passive and carrier-mediated processes in drug transport. Nat. Rev. Drug Discov. 9, 597-614.
38. Tachi, M., Imanishi, S. Y., and Harada, K. (2007). Phosphoprotein analysis for investigation of in vivo relationship between protein phosphatase inhibitory activities and acute hepatotoxicity of microcystin-LR. Environ. Toxicol. 22, 620-629.
39. Toivola, D. M., Eriksson, J. E., and Brautigan, D. L. (1994). Identification of protein phosphatase 2A as the primary target for microcystin-LR in rat liver homogenates. FEBS Lett. 344, 175-180.
40. Ulvestad, M., Björquist, P., Molden, E., Asberg, A., and Andersson, T. B. (2011). OATP1B1/1B3 activity in plated primary human hepatocytes over time in culture. Biochem. Pharmacol. 82, 1219-1226.
41. van de Steeg, E., Stranecky, V., Hartmannova, H., Noskova, L., Hrebicek, M., Wagenaar, E., van Esch, A., de Waart, D. R., Oude Elferink, R. P., Kenworthy, K. E., et al. (2012). Complete OATP1B1 and OATP1B3 deficiency causes human Rotor syndrome by interrupting conjugated bilirubin reuptake into the liver. J Clin. Invest. 122, 519-528.
42. van de Waterbeemd, H., and Gifford, E. (2003). ADMET in silico modelling: Towards prediction paradise? Nat. Rev. Drug Discov. 2, 192-204.
43. Vander Borght, S., Libbrecht, L., Blokzijl, H., Faber, K. N., Moshage, H., Aerts, R., Van Steenbergen, W., Jansen, P. L., Desmet, V. J., and Roskams, T. A. (2005). Diagnostic and pathogenetic implications of the expression of hepatic transporters in focal lesions occurring in normal liver. J. Pathol. 207, 471-482.
44. Venter, J. C., Adams, M. D., Myers, E. W., Li, P. W., Mural, R. J., Sutton, G. G., Smith, H. O., Yandell, M., Evans, C. A., Holt, R. A., et al. (2001). The sequence of the human genome. Science 291, 1304-1351.
45. Wong, C. C., Botting, N. P., Orfila, C., Al-Maharik, N., and Williamson, G. (2011). Flavonoid conjugates interact with organic anion transporters (OATs) and attenuate cytotoxicity of adefovir mediated by organic anion transporter 1 (OAT1/SLC22A6). Biochem. Pharmacol. 81, 942-949.
46. Zaher, H., Meyer zu Schwabedissen, H. E., Tirona, R. G., Cox, M. L., Obert, L. A., Agrawal, N., Palandra, J., Stock, J. L., Kim, R. B., and Ware, J. A. (2008). Targeted disruption of murine organic anion-transporting polypeptide 1b2 (Oatp1b2/Slco1b2) significantly alters disposition of prototypical drug substrates pravastatin and rifampin. Mol. Pharmacol. 74, 320-329.
47. Zolk, O., and Fromm, M. F. (2011). Transporter-mediated drug uptake and efflux: Important determinants of adverse drug reactions. Clin. Pharmacol. Ther. 89, 798-805.