Table of Contents Author Guidelines Submit a Manuscript
Scientifica
Volume 2012, Article ID 428139, 15 pages
http://dx.doi.org/10.6064/2012/428139
Review Article

Plasma Membrane Transporters in Modern Liver Pharmacology

1Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, University of Salamanca and CIBERehd, Spain
2Department of Physiology and Pharmacology, Campus Miguel de Unamuno E.D. S09, 37007 Salamanca, Spain

Received 23 August 2012; Accepted 26 September 2012

Academic Editors: P. O. Gubbins and V. S. Subramanian

Copyright © 2012 Jose J. G. Marin. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. Y. Sai and A. Tsuji, “Transporter-mediated drug delivery: recent progress and experimental approaches,” Drug Discovery Today, vol. 9, no. 16, pp. 712–720, 2004. View at Publisher · View at Google Scholar · View at Scopus
  2. Y. Huang and W. Sadée, “Membrane transporters and channels in chemoresistance and -sensitivity of tumor cells,” Cancer Letters, vol. 239, no. 2, pp. 168–182, 2006. View at Publisher · View at Google Scholar · View at Scopus
  3. M. Nicolaou, E. J. Andress, J. K. Zolnerciks, P. H. Dixon, C. Williamson, and K. J. Linton, “Canalicular ABC transporters and liver disease,” The Journal of Pathology, vol. 226, pp. 300–315, 2012. View at Google Scholar
  4. J. J. G. Marin, M. R. Romero, P. Martinez-Becerra, E. Herraez, and O. Briz, “Overview of the molecular bases of resistance to chemotherapy in liver and gastrointestinal tumours,” Current Molecular Medicine, vol. 9, no. 9, pp. 1108–1129, 2009. View at Publisher · View at Google Scholar · View at Scopus
  5. J. J. Marin, O. Briz, M. J. Monte, A. G. Blazquez, and R. I. Macias, “Genetic variants in genes involved in mechanisms of chemoresistance to anticancer drugs,” Current Cancer Drug Targets, vol. 12, pp. 402–438, 2012. View at Google Scholar
  6. O. Zolk and M. F. Fromm, “Transporter-mediated drug uptake and efflux: Important determinants of adverse drug reactions,” Clinical Pharmacology and Therapeutics, vol. 89, no. 6, pp. 798–805, 2011. View at Publisher · View at Google Scholar · View at Scopus
  7. L. Rodríguez-Fragoso, J. L. Martínez-Arismendi, D. Orozco-Bustos, J. Reyes-Esparza, E. Torres, and S. W. Burchiel, “Potential risks resulting from fruit/vegetable-drug interactions: effects on drug-metabolizing enzymes and drug transporters,” Journal of Food Science, vol. 76, no. 4, pp. R112–R124, 2011. View at Publisher · View at Google Scholar · View at Scopus
  8. H. Hayashi, K. Inamura, K. Aida et al., “AP2 adaptor complex mediates bile salt export pump internalization and modulates its hepatocanalicular expression and transport function,” Hepatology, vol. 55, pp. 1889–1900, 2012. View at Google Scholar
  9. M. K. Leabman, C. C. Huang, J. DeYoung et al., “Natural variation in human membrane transporter genes reveals evolutionary and functional constraints,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 10, pp. 5896–5901, 2003. View at Publisher · View at Google Scholar · View at Scopus
  10. B. Hagenbuch and P. J. Meier, “Organic anion transporting polypeptides of the OATP/SLC21 family: phylogenetic classification as OATP/SLCO super-family, new nomenclature and molecular/functional properties,” Pflugers Archiv European Journal of Physiology, vol. 447, no. 5, pp. 653–665, 2004. View at Publisher · View at Google Scholar · View at Scopus
  11. C. D. Klaassen and L. M. Aleksunes, “Xenobiotic, bile acid, and cholesterol transporters: function and regulation,” Pharmacological Reviews, vol. 62, no. 1, pp. 1–96, 2010. View at Publisher · View at Google Scholar · View at Scopus
  12. S. Leuthold, B. Hagenbuch, N. Mohebbi, C. A. Wagner, P. J. Meier, and B. Stieger, “Mechanisms of pH-gradient driven transport mediated by organic anion polypeptide transporters,” American Journal of Physiology—Cell Physiology, vol. 296, no. 3, pp. C570–C582, 2009. View at Publisher · View at Google Scholar · View at Scopus
  13. P. Martinez-Becerra, O. Briz, M. R. Romero et al., “Further characterization of the electrogenicity and ph sensitivity of the human organic anion-transporting polypeptides OATP1B1 and OATP1B3,” Molecular Pharmacology, vol. 79, no. 3, pp. 596–607, 2011. View at Publisher · View at Google Scholar · View at Scopus
  14. M. Okabe, G. Szakács, M. A. Reimers et al., “Profiling SLCO and SLC22 genes in the NCI-60 cancer cell lines to identify drug uptake transporters,” Molecular Cancer Therapeutics, vol. 7, no. 9, pp. 3081–3091, 2008. View at Publisher · View at Google Scholar · View at Scopus
  15. T. Nozawa, H. Minami, S. Sugiura, A. Tsuji, and I. Tamai, “Role of organic anion transporter OATP1B1 (OATP-C) in hepatic uptake of irinotecan and its active metabolite, 7-ethyl-10-hydroxycamptothecin: in vitro evidence and effect of single nucleotide polymorphisms,” Drug Metabolism and Disposition, vol. 33, no. 3, pp. 434–439, 2005. View at Publisher · View at Google Scholar · View at Scopus
  16. W. Ni, J. Ji, Z. Dai et al., “Flavopiridol pharmacogenetics: clinical and functional evidence for the role of SLCO1B1/OATP1B1 in flavopiridol disposition,” PLoS ONE, vol. 5, no. 11, Article ID e13792, 2010. View at Publisher · View at Google Scholar · View at Scopus
  17. L. B. Ramsey, G. H. Bruun, W. Yang et al., “Rare versus common variants in pharmacogenetics: SLCO1B1 variation and methotrexate disposition,” Genome Research, vol. 22, pp. 1–8, 2012. View at Google Scholar
  18. M. Svoboda, K. Wlcek, B. Taferner et al., “Expression of organic anion-transporting polypeptides 1B1 and 1B3 in ovarian cancer cells: relevance for paclitaxel transport,” Biomedicine and Pharmacotherapy, vol. 65, no. 6, pp. 417–426, 2011. View at Publisher · View at Google Scholar · View at Scopus
  19. O. Briz, M. A. Serrano, N. Rebollo et al., “Carriers involved in targeting the cytostatic bile acid-cisplatin derivatives cis-diammine-chloro-cholylglycinate-platinum(II) and cis-diammine-bisursodeoxycholate-platinum(II) toward liver cells,” Molecular Pharmacology, vol. 61, no. 4, pp. 853–860, 2002. View at Publisher · View at Google Scholar · View at Scopus
  20. S. Seki, M. Kobayashi, S. Itagaki, T. Hirano, and K. Iseki, “Contribution of organic anion transporting polypeptide OATP2B1 to amiodarone accumulation in lung epithelial cells,” Biochimica et Biophysica Acta, vol. 1788, no. 5, pp. 911–917, 2009. View at Publisher · View at Google Scholar · View at Scopus
  21. M. Visentin, M. H. Chang, M. F. Romero, R. Zhao, and I. D. Goldman, “Substrate- and pH-specific antifolate transport mediated by organic anion-transporting polypeptide 2B1 (OATP2B1-SLCO2B1),” Molecular Pharmacology, vol. 81, pp. 134–142, 2012. View at Google Scholar
  22. W. Lee, H. Glaeser, L. H. Smith et al., “Polymorphisms in human organic anion-transporting polypeptide 1A2 (OATP1A2): implications for altered drug disposition and central nervous system drug entry,” Journal of Biological Chemistry, vol. 280, no. 10, pp. 9610–9617, 2005. View at Publisher · View at Google Scholar · View at Scopus
  23. I. Badagnani, R. A. Castro, T. R. Taylor et al., “Interaction of methotrexate with organic-anion transporting polypeptide 1A2 and its genetic variants,” Journal of Pharmacology and Experimental Therapeutics, vol. 318, no. 2, pp. 521–529, 2006. View at Publisher · View at Google Scholar · View at Scopus
  24. Y. Yamakawa, A. Hamada, T. Shuto et al., “Pharmacokinetic impact of SLCO1A2 polymorphisms on imatinib disposition in patients with chronic myeloid Leukemia,” Clinical Pharmacology and Therapeutics, vol. 90, no. 1, pp. 157–163, 2011. View at Publisher · View at Google Scholar · View at Scopus
  25. H. K. Han, “Role of transporters in drug interactions,” Archives of Pharmacal Research, vol. 34, pp. 1865–1877, 2011. View at Google Scholar
  26. M. Cvetkovic, B. Leake, M. F. Fromm, G. R. Wilkinson, and R. B. Kim, “OATP and P-glycoprotein transporters mediate the cellular uptake and excretion of fexofenadine,” Drug Metabolism and Disposition, vol. 27, no. 8, pp. 866–871, 1999. View at Google Scholar · View at Scopus
  27. G. K. Dresser, D. G. Bailey, B. F. Leake et al., “Fruit juices inhibit organic anion transporting polypeptide-mediated drug uptake to decrease the oral availability of fexofenadine,” Clinical Pharmacology and Therapeutics, vol. 71, no. 1, pp. 11–20, 2002. View at Publisher · View at Google Scholar · View at Scopus
  28. H. Satoh, F. Yamashita, M. Tsujimoto et al., “Citrus juices inhibit the function of human organic anion-transporting polypeptide OATP-B,” Drug Metabolism and Disposition, vol. 33, no. 4, pp. 518–523, 2005. View at Publisher · View at Google Scholar · View at Scopus
  29. Y. Shitara, M. Hirano, H. Sato, and Y. Sugiyama, “Gemfibrozil and its glucoronide inhibit the organic anion transporting polypeptide 2 (OATP2/OATP1B1:SLC21A6)-mediated hepatic uptake and CYP2C8-mediated metabolism of cerivastatin: analysis of the mechanism of the clinically relevant drug-drug interaction between cerivastatin and gemfibrozil,” Journal of Pharmacology and Experimental Therapeutics, vol. 311, no. 1, pp. 228–236, 2004. View at Publisher · View at Google Scholar · View at Scopus
  30. M. Yamazaki, B. Li, S. W. Louie et al., “Effects of fibrates on human organic anion-transporting polypeptide 1B1-, multidrug resistance protein 2- and P-glycoprotein-mediated transport,” Xenobiotica, vol. 35, no. 7, pp. 737–753, 2005. View at Publisher · View at Google Scholar · View at Scopus
  31. Y. Y. Lau, Y. Huang, L. Frassetto, and L. Z. Benet, “Effect of OATP1B transporter inhibition on the pharmacokinetics of atorvastatin in healthy volunteers,” Clinical Pharmacology and Therapeutics, vol. 81, no. 2, pp. 194–204, 2007. View at Publisher · View at Google Scholar · View at Scopus
  32. J. D. Clarke and N. J. Cherrington, “Genetics or environment in drug transport: the case of organic anion transporting polypeptides and adverse drug reactions,” Expert Opinion on Drug Metabolism & Toxicology, vol. 8, pp. 349–360, 2012. View at Google Scholar
  33. R. I. Macias, C. Hierro, S. C. de Juan, F. Jimenez, F. Gonzalez-San Martin, and J. J. Marin, “Hepatic expression of sodium-dependent vitamin C transporters: ontogeny, subtissular distribution and effect of chronic liver diseases,” British Journal of Nutrition, vol. 106, pp. 1814–1825, 2011. View at Google Scholar
  34. P. Martinez-Becerra, J. Vaquero, M. R. Romero et al., “No correlation between the expression of FXR and genes involved in multidrug resistance phenotype of primary liver tumors,” Molecular Pharmacology, vol. 9, pp. 1693–1704, 2012. View at Google Scholar
  35. R. G. Tirona, B. F. Leake, G. Merino, and R. B. Kim, “Polymorphisms in OATP-C: identification of multiple allelic variants associated with altered transport activity among European- and African-Americans,” Journal of Biological Chemistry, vol. 276, no. 38, pp. 35669–35675, 2001. View at Publisher · View at Google Scholar · View at Scopus
  36. M. K. Pasanen, M. Neuvonen, P. J. Neuvonen, and M. Niemi, “SLCO1B1 polymorphism markedly affects the pharmacokinetics of simvastatin acid,” Pharmacogenetics and Genomics, vol. 16, no. 12, pp. 873–879, 2006. View at Publisher · View at Google Scholar · View at Scopus
  37. E. Link, S. Parish, J. Armitage et al., “SLCO1B1 variants and statin-induced myopathy—a genomewide study,” The New England Journal of Medicine, vol. 359, no. 8, pp. 789–799, 2008. View at Publisher · View at Google Scholar · View at Scopus
  38. H. Michelon, J. König, A. Durrbach et al., “SLCO1B1 genetic polymorphism influences mycophenolic acid tolerance in renal transplant recipients,” Pharmacogenomics, vol. 11, no. 12, pp. 1703–1713, 2010. View at Publisher · View at Google Scholar · View at Scopus
  39. N. Picard, S. W. Yee, J. B. Woillard et al., “The role of organic anion-transporting polypeptides and their common genetic variants in mycophenolic acid pharmacokinetics,” Clinical Pharmacology and Therapeutics, vol. 87, no. 1, pp. 100–108, 2010. View at Publisher · View at Google Scholar · View at Scopus
  40. E. Herraez, R. I. R. Macias, J. Vazquez-Tato, M. Vicens, M. J. Monte, and J. J. G. Marin, “In vitro inhibition of OATP-mediated uptake of phalloidin using bile acid derivatives,” Toxicology and Applied Pharmacology, vol. 239, no. 1, pp. 13–20, 2009. View at Publisher · View at Google Scholar · View at Scopus
  41. E. Herraez, R. I. R. Macias, J. Vazquez-Tato, C. Hierro, M. J. Monte, and J. J. G. Marin, “Protective effect of bile acid derivatives in phalloidin-induced rat liver toxicity,” Toxicology and Applied Pharmacology, vol. 239, no. 1, pp. 21–28, 2009. View at Publisher · View at Google Scholar · View at Scopus
  42. R. Zhao, N. Diop-Bove, M. Visentin, and I. D. Goldman, “Mechanisms of membrane transport of folates into cells and across epithelia,” Annual Review of Nutrition, vol. 31, pp. 177–201, 2011. View at Publisher · View at Google Scholar · View at Scopus
  43. J. A. Moscow, M. Gong, R. He et al., “Isolation of a gene encoding a human reduced folate carrier (RFC1) and analysis of its expression in transport-deficient, methotrexate-resistant human breast cancer cells,” Cancer Research, vol. 55, no. 17, pp. 3790–3794, 1995. View at Google Scholar · View at Scopus
  44. J. Gregers, I. J. Christensen, K. Dalhoff et al., “The association of reduced folate carrier 80G > A polymorphism to outcome in childhood acute lymphoblastic leukemia interacts with chromosome 21 copy number,” Blood, vol. 115, no. 23, pp. 4671–4677, 2010. View at Publisher · View at Google Scholar · View at Scopus
  45. L. Rothem, I. Ifergan, Y. Kaufman, D. G. Priest, G. Jansen, and Y. G. Assaraf, “Resistance to multiple novel antifolates is mediated via defective drug transport resulting from clustered mutations in the reduced folate carrier gene in human leukaemia cell lines,” Biochemical Journal, vol. 367, no. 3, pp. 741–750, 2002. View at Publisher · View at Google Scholar · View at Scopus
  46. H. Miyazaki, T. Sekine, and H. Endou, “The multispecific organic anion transporter family: properties and pharmacological significance,” Trends in Pharmacological Sciences, vol. 25, no. 12, pp. 654–662, 2004. View at Publisher · View at Google Scholar · View at Scopus
  47. W. Sun, R. R. Wu, P. D. Van Poelje, and M. D. Erion, “Isolation of a family of organic anion transporters from human liver and kidney,” Biochemical and Biophysical Research Communications, vol. 283, no. 2, pp. 417–422, 2001. View at Publisher · View at Google Scholar · View at Scopus
  48. G. Burckhardt, “Drug transport by Organic Anion Transporters (OATs),” Pharmacology & Therapeutics, vol. 136, no. 1, pp. 106–130, 2012. View at Google Scholar
  49. Y. Kobayashi, N. Ohshiro, R. Sakai, M. Ohbayashi, N. Kohyama, and T. Yamamoto, “Transport mechanism and substrate specificity of human organic anion transporter 2 (hOat2 [SLC22A7]),” Journal of Pharmacy and Pharmacology, vol. 57, no. 5, pp. 573–578, 2005. View at Publisher · View at Google Scholar · View at Scopus
  50. E. J. Jeong, H. Lin, and M. Hu, “Disposition mechanisms of raloxifene in the human intestinal Caco-2 model,” Journal of Pharmacology and Experimental Therapeutics, vol. 310, no. 1, pp. 376–385, 2004. View at Publisher · View at Google Scholar · View at Scopus
  51. H. Koepsell, K. Lips, and C. Volk, “Polyspecific organic cation transporters: structure, function, physiological roles, and biopharmaceutical implications,” Pharmaceutical Research, vol. 24, no. 7, pp. 1227–1251, 2007. View at Publisher · View at Google Scholar · View at Scopus
  52. G. Burckhardt and N. A. Wolff, “Structure of renal organic anion and cation transporters,” American Journal of Physiology—Renal Physiology, vol. 278, no. 6, pp. F853–F866, 2000. View at Google Scholar · View at Scopus
  53. G. G. Graham, J. Punt, M. Arora et al., “Clinical pharmacokinetics of metformin,” Clinical Pharmacokinetics, vol. 50, no. 2, pp. 81–98, 2011. View at Publisher · View at Google Scholar · View at Scopus
  54. M. K. DeGorter, C. Q. Xia, J. J. Yang, and R. B. Kim, “Drug transporters in drug efficacy and toxicity,” Annual Review of Pharmacology and Toxicology, vol. 52, pp. 249–273, 2012. View at Google Scholar
  55. A. M. Lamhonwah and I. Tein, “Novel localization of OCTN1, an organic cation/carnitine transporter, to mammalian mitochondria,” Biochemical and Biophysical Research Communications, vol. 345, no. 4, pp. 1315–1325, 2006. View at Publisher · View at Google Scholar · View at Scopus
  56. J. J. G. Marin, B. Castaño, A. G. Blazquez, R. Rosales, T. Efferth, and M. J. Monte, “Strategies for overcoming chemotherapy resistance in enterohepatic tumours,” Current Molecular Medicine, vol. 10, no. 5, pp. 467–485, 2010. View at Publisher · View at Google Scholar · View at Scopus
  57. L. Wang, A. Giannoudis, S. Lane, P. Williamson, M. Pirmohamed, and R. E. Clark, “Expression of the uptake drug transporter hOCT1 is an important clinical determinant of the response to imatinib in chronic myeloid leukemia,” Clinical Pharmacology and Therapeutics, vol. 83, no. 2, pp. 258–264, 2008. View at Publisher · View at Google Scholar · View at Scopus
  58. S. Gupta, G. Wulf, M. Henjakovic, H. Koepsell, G. Burckhardt, and Y. Hagos, “Human Organic Cation Transporter 1 is expressed in lymphoma cells and increases the susceptibility to irinotecan and paclitaxel,” Journal of Pharmacology and Experimental Therapeutics, vol. 341, pp. 16–23, 2012. View at Google Scholar
  59. Q. Q. Huang, S. Y. M. Yao, M. W. L. Ritzel, A. R. P. Paterson, C. E. Cass, and J. D. Young, “Cloning and functional expression of a complementary DNA encoding a mammalian nucleoside transport protein,” Journal of Biological Chemistry, vol. 269, no. 27, pp. 17757–17760, 1994. View at Google Scholar · View at Scopus
  60. M. W. L. Ritzel, S. Y. M. Yao, A. M. L. Ng, J. R. Mackey, C. E. Cass, and J. D. Young, “Molecular cloning, functional expression and chromosomal localization of a cDNA encoding a human Na+/nucleoside cotransporter (hCNT2) selective for purine nucleosides and uridine,” Molecular Membrane Biology, vol. 15, no. 4, pp. 203–211, 1998. View at Google Scholar · View at Scopus
  61. S. Y. M. Yao, A. M. L. Ng, W. R. Muzyka et al., “Molecular cloning and functional characterization of nitrobenzylthioinosine (NBMPR)-sensitive (es) and NBMPR-insensitive (ei) equilibrative nucleoside transporter proteins (rENT1 and rENT2) from rat tissues,” Journal of Biological Chemistry, vol. 272, no. 45, pp. 28423–28430, 1997. View at Publisher · View at Google Scholar · View at Scopus
  62. C. R. Crawford, D. H. Patel, C. Naeve, and J. A. Belt, “Cloning of the human equilibrative, nitrobenzylmercaptopurine riboside (NBMPR)-insensitive nucleoside transporter ei by functional expression in a transport-deficient cell line,” Journal of Biological Chemistry, vol. 273, no. 9, pp. 5288–5293, 1998. View at Publisher · View at Google Scholar · View at Scopus
  63. S. Mori, S. Ohtsuki, H. Takanaga, T. Kikkawa, Y. S. Kang, and T. Terasaki, “Organic anion transporter 3 is involved in the brain-to-blood efflux transport of thiopurine nucleobase analogs,” Journal of Neurochemistry, vol. 90, no. 4, pp. 931–941, 2004. View at Publisher · View at Google Scholar · View at Scopus
  64. D. Santini, G. Schiavon, B. Vincenzi et al., “Human equilibrative nucleoside transporter 1 (hENT1) levels predict response to gemcitabine in patients with biliary tract cancer (BTC),” Current Cancer Drug Targets, vol. 11, no. 1, pp. 123–129, 2011. View at Publisher · View at Google Scholar · View at Scopus
  65. K. D. Ibarra and J. K. Pfeiffer, “Reduced ribavirin antiviral efficacy via nucleoside transporter-mediated drug resistance,” Journal of Virology, vol. 83, no. 9, pp. 4538–4547, 2009. View at Publisher · View at Google Scholar · View at Scopus
  66. F. Molina-Jimenez, I. Benedicto, V. L. Dao Thi et al., “Matrigel-embedded 3D culture of Huh-7 cells as a hepatocyte-like polarized system to study hepatitis C virus cycle,” Virology, vol. 425, pp. 31–39, 2012. View at Google Scholar
  67. Y. J. Fei, Y. Kanai, S. Nussberger et al., “Expression cloning of a mammalian proton-coupled oligopeptide transporter,” Nature, vol. 368, no. 6471, pp. 563–566, 1994. View at Publisher · View at Google Scholar · View at Scopus
  68. W. Liu, R. Liang, S. Ramamoorthy et al., “Molecular cloning of PEPT 2, a new member of the H+/peptide cotransporter family, from human kidney,” Biochimica et Biophysica Acta, vol. 1235, no. 2, pp. 461–466, 1995. View at Publisher · View at Google Scholar · View at Scopus
  69. J. Lee, M. M. O. Peña, Y. Nose, and D. J. Thiele, “Biochemical characterization of the human copper transporter Ctr1,” Journal of Biological Chemistry, vol. 277, no. 6, pp. 4380–4387, 2002. View at Publisher · View at Google Scholar · View at Scopus
  70. E. M. Rees, J. Lee, and D. J. Thiele, “Mobilization of intracellular copper stores by the Ctr2 vacuolar copper transporter,” Journal of Biological Chemistry, vol. 279, no. 52, pp. 54221–54229, 2004. View at Publisher · View at Google Scholar · View at Scopus
  71. R. Safaei and S. B. Howell, “Copper transporters regulate the cellular pharmacology and sensitivity to Pt drugs,” Critical Reviews in Oncology/Hematology, vol. 53, no. 1, pp. 13–23, 2005. View at Publisher · View at Google Scholar · View at Scopus
  72. M. J. Monte, M. R. Ballestero, O. Briz, M. J. Perez, and J. J. G. Marin, “Proapoptotic effect on normal and tumor intestinal cells of cytostatic drugs with enterohepatic organotropism,” Journal of Pharmacology and Experimental Therapeutics, vol. 315, no. 1, pp. 24–35, 2005. View at Publisher · View at Google Scholar · View at Scopus
  73. B. G. Blair, C. A. Larson, P. L. Adams et al., “Copper transporter 2 regulates endocytosis and controls tumor growth and sensitivity to cisplatin in vivo,” Molecular Pharmacology, vol. 79, no. 1, pp. 157–166, 2011. View at Publisher · View at Google Scholar · View at Scopus
  74. J. J. G. Marin, O. Briz, M. J. Perez, M. R. Romero, and M. J. Monte, “Hepatobiliary transporters in the pharmacology and toxicology of anticancer drugs,” Frontiers in Bioscience, vol. 14, no. 11, pp. 4257–4280, 2009. View at Publisher · View at Google Scholar · View at Scopus
  75. N. F. H. Ho, “Utilizing bile acid carrier mechanisms to enhance liver and small intestine absorption,” Annals of the New York Academy of Sciences, vol. 507, pp. 315–329, 1987. View at Google Scholar · View at Scopus
  76. D. A. Betebenner, P. L. Carney, A. M. Zimmer et al., “Hepatobiliary delivery of polyaminopolycarboxylate chelates: synthesis and characterization of a cholic acid conjugate of EDTA and biodistribution and imaging studies with its indium-111 chelate,” Bioconjugate Chemistry, vol. 2, no. 2, pp. 117–123, 1991. View at Google Scholar · View at Scopus
  77. Z. F. Stephan, E. C. Yurachek, R. Sharif, J. M. Wasvary, R. E. Steele, and C. Howes, “Reduction of cardiovascular and thyroxine-suppressing activities of L-T3 by liver targeting with cholic acid,” Biochemical Pharmacology, vol. 43, no. 9, pp. 1969–1974, 1992. View at Publisher · View at Google Scholar · View at Scopus
  78. W. Kramer and G. Wess, “Bile acid transport systems as pharmaceutical targets,” European Journal of Clinical Investigation, vol. 26, no. 9, pp. 715–732, 1996. View at Google Scholar · View at Scopus
  79. M. J. Monte, S. Dominguez, M. F. Palomero, R. I. R. Macias, and J. J. G. Marin, “Further evidence of the usefulness of bile acids as molecules for shuttling cytostatic drugs toward liver tumors,” Journal of Hepatology, vol. 31, no. 3, pp. 521–528, 1999. View at Publisher · View at Google Scholar · View at Scopus
  80. W. Kramer, F. Girbig, H. Glombik, D. Corsiero, S. Stengelin, and C. Weyland, “Identification of a ligand-binding site in the Na+/Bile acid cotransporting protein from rabbit ileum,” Journal of Biological Chemistry, vol. 276, no. 38, pp. 36020–36027, 2001. View at Publisher · View at Google Scholar · View at Scopus
  81. G. A. Kullak-Ublick, J. Glasa, C. Boker et al., “Chlorambucil-taurocholate is transported by bile acid carriers expressed in human hepatocellular carcinomas,” Gastroenterology, vol. 113, no. 4, pp. 1295–1305, 1997. View at Publisher · View at Google Scholar · View at Scopus
  82. E. O. Im, Y. H. Choi, K. J. Paik et al., “Novel bile acid derivatives induce apoptosis via a p53-independent pathway in human breast carcinoma cells,” Cancer Letters, vol. 163, no. 1, pp. 83–93, 2001. View at Publisher · View at Google Scholar · View at Scopus
  83. J. J. Criado, M. F. Domínguez, M. Medarde, E. R. Fernández, R. I. R. Macías, and J. J. G. Marín, “Structural characterization, kinetic studies, and in vitro biological activity of new cis-diamminebis-cholylglycinate(O,O') Pt(II) and cis-diamminebis-ursodeoxycholate(O,O') Pt(II) complexes,” Bioconjugate Chemistry, vol. 11, no. 2, pp. 167–174, 2000. View at Publisher · View at Google Scholar · View at Scopus
  84. J. J. Criado, M. C. Herrera, M. F. Palomero, M. Medarde, E. Rodriguez, and J. J. G. Marin, “Synthesis and characterization of a new bile acid and platinum(II) complex with cytostatic activity,” Journal of Lipid Research, vol. 38, no. 5, pp. 1022–1032, 1997. View at Google Scholar · View at Scopus
  85. J. J. Criado, M. C. Garcia-Moreno, R. R. Macias, J. J. G. Marin, M. Medarde, and E. Rodriguez-Fernandez, “Synthesis and characterization of sodium cis-dichlorochenodeoxycholylglycinato(O,N) platinum(II)- Cytostatic activity,” BioMetals, vol. 12, no. 3, pp. 281–288, 1999. View at Google Scholar · View at Scopus
  86. J. J. Criado, R. I. R. Macias, M. Medarde, M. J. Monte, M. A. Serrano, and J. J. G. Marin, “Synthesis and characterization of the new cytostatic complex cis-diammineplatinum(II)-chlorocholylglycinate,” Bioconjugate Chemistry, vol. 8, no. 4, pp. 453–458, 1997. View at Publisher · View at Google Scholar · View at Scopus
  87. J. Carrasco, J. J. Criado, R. I. R. Macías et al., “Structural characterization and cytostatic activity of chlorobischolylglycinatogold(III),” Journal of Inorganic Biochemistry, vol. 84, no. 3-4, pp. 287–292, 2001. View at Google Scholar · View at Scopus
  88. F. M. Muggia, “Cisplatin update,” Seminars in Oncology, vol. 18, no. 1, pp. 1–4, 1991. View at Google Scholar · View at Scopus
  89. N. Maeda, N. Takasuka, T. Suga, and T. Sasaki, “New antitumor platinum(II) complexes with both lipophilicity and water miscibility,” Japanese Journal of Cancer Research, vol. 81, no. 6-7, pp. 567–569, 1990. View at Google Scholar · View at Scopus
  90. R. I. R. Macias, M. J. Monte, M. Y. El-Mir, G. R. Villanueva, and J. J. G. Marin, “Transport and biotransformation of the new cytostatic complex cis- diammineplatinum(II)-chlorocholylglycinate (Bamet-R2) by the rat liver,” Journal of Lipid Research, vol. 39, no. 9, pp. 1792–1798, 1998. View at Google Scholar · View at Scopus
  91. M. G. Larena, M. C. Martinez-Diez, M. J. Monte, M. F. Dominguez, M. J. Pascual, and J. J. G. Marin, “Liver organotropism and biotransformation of a novel platinum-ursodeoxycholate derivative, Bamet-UD2, with enhanced antitumour activity,” Journal of Drug Targeting, vol. 9, no. 3, pp. 185–200, 2001. View at Google Scholar · View at Scopus
  92. L. M. S. Chan, S. Lowes, and B. H. Hirst, “The ABCs of drug transport in intestine and liver: efflux proteins limiting drug absorption and bioavailability,” European Journal of Pharmaceutical Sciences, vol. 21, no. 1, pp. 25–51, 2004. View at Publisher · View at Google Scholar · View at Scopus
  93. M. J. Perez, E. Gonzalez-Sanchez, A. Gonzalez-Loyola, J. M. Gonzalez-Buitrago, and J. J. G. Marin, “Mitochondrial genome depletion dysregulates bile acid- and paracetamol-induced expression of the transporters Mdr1, Mrp1 and Mrp4 in liver cells,” British Journal of Pharmacology, vol. 162, no. 8, pp. 1686–1699, 2011. View at Publisher · View at Google Scholar · View at Scopus
  94. I. Cascorbi, “P-glycoprotein: tissue distribution, substrates, and functional consequences of genetic variations,” Handbook of Experimental Pharmacology, vol. 201, pp. 261–283, 2011. View at Publisher · View at Google Scholar · View at Scopus
  95. X. Chenivesse, D. Franco, and C. Brechot, “MDR1 (multidrug resistance) gene expression in human primary liver cancer and cirrhosis,” Journal of Hepatology, vol. 18, no. 2, pp. 168–172, 1993. View at Google Scholar · View at Scopus
  96. I. O. L. Ng, C. L. Liu, S. T. Fan, and M. Ng, “Expression of P-glycoprotein in hepatocellular carcinoma: a determinant of chemotherapy response,” American Journal of Clinical Pathology, vol. 113, no. 3, pp. 355–363, 2000. View at Google Scholar · View at Scopus
  97. A. Kato, M. Miyazaki, S. Ambiru et al., “Multidrug resistance gene (MDR-1) expression as a useful prognostic factor in patients with human hepatocellular carcinoma after surgical resection,” Journal of Surgical Oncology, vol. 78, pp. 110–115, 2001. View at Google Scholar
  98. P. Grudé, F. Conti, D. Mennecier et al., “MDR1 gene expression in hepatocellular carcinoma and the peritumoral liver of patients with and without cirrhosis,” Cancer Letters, vol. 186, no. 1, pp. 107–113, 2002. View at Publisher · View at Google Scholar · View at Scopus
  99. M. J. Monte, J. J. G. Marin, A. Antelo, and J. Vazquez-Tato, “Bile acids: chemistry, physiology, and pathophysiology,” World Journal of Gastroenterology, vol. 15, no. 7, pp. 804–816, 2009. View at Publisher · View at Google Scholar · View at Scopus
  100. B. Stieger, “Role of the bile salt export pump, BSEP, in acquired forms of cholestasis,” Drug Metabolism Reviews, vol. 42, no. 3, pp. 437–445, 2010. View at Publisher · View at Google Scholar · View at Scopus
  101. M. Vallejo, O. Briz, M. A. Serrano, M. J. Monte, and J. J. G. Marin, “Potential role of trans-inhibition of the bile salt export pump by progesterone metabolites in the etiopathogenesis of intrahepatic cholestasis of pregnancy,” Journal of Hepatology, vol. 44, no. 6, pp. 1150–1157, 2006. View at Publisher · View at Google Scholar · View at Scopus
  102. B. Stieger, K. Fattinger, J. Madon, G. A. Kullak-Ublick, and P. J. Meier, “Drug- and estrogen-induced cholestasis through inhibition of the hepatocellular bile salt export pump (Bsep) of rat liver,” Gastroenterology, vol. 118, no. 2, pp. 422–430, 2000. View at Google Scholar · View at Scopus
  103. R. Rosales, M. J. Monte, A. G. Blazquez, O. Briz, and J. J. G. Marin, “ABCC2 is involved in the hepatocyte perinuclear barrier for small organic compounds,” Biochemical Pharmacology. In press.
  104. J. J. G. Marin, M. R. Romero, and O. Briz, “Molecular bases of liver cancer refractoriness to pharmacological treatment,” Current Medicinal Chemistry, vol. 17, no. 8, pp. 709–740, 2010. View at Publisher · View at Google Scholar · View at Scopus
  105. A. T. Nies, J. König, M. Pfannschmidt, E. Klar, W. J. Hofmann, and D. Keppler, “Expression of the multidrug resistance proteins MRP2 and MRP3 in human hepatocellular carcinoma,” International Journal of Cancer, vol. 94, no. 4, pp. 492–499, 2001. View at Publisher · View at Google Scholar · View at Scopus
  106. G. Zollner, M. Wagner, P. Fickert et al., “Hepatobiliary transporter expression in human hepatocellular carcinoma,” Liver International, vol. 25, no. 2, pp. 367–379, 2005. View at Publisher · View at Google Scholar · View at Scopus
  107. A. T. Nies and D. Keppler, “The apical conjugate efflux pump ABCC2 (MRP2),” Pflugers Archiv European Journal of Physiology, vol. 453, no. 5, pp. 643–659, 2007. View at Publisher · View at Google Scholar · View at Scopus
  108. R. G. Deeley and S. P. C. Cole, “Substrate recognition and transport by multidrug resistance protein 1 (ABCC1),” FEBS Letters, vol. 580, no. 4, pp. 1103–1111, 2006. View at Publisher · View at Google Scholar · View at Scopus
  109. R. Allikmets, L. M. Schriml, A. Hutchinson, V. Romano-Spica, and M. Dean, “A human placenta-specific ATP-binding cassette gene (ABCP) on chromosome 4q22 that is involved in multidrug resistance,” Cancer Research, vol. 58, no. 23, pp. 5337–5339, 1998. View at Google Scholar · View at Scopus
  110. A. G. Blazquez, O. Briz, M. R. Romero et al., “Characterization of the role of ABCG2 as a bile acid transporter in liver and placenta,” Molecular Pharmacology, vol. 81, pp. 273–283, 2012. View at Google Scholar
  111. Z. Ni, Z. Bikadi, M. F. Rosenberg, and Q. Mao, “Structure and function of the human breast cancer resistance protein (BCRP/ABCG2),” Current Drug Metabolism, vol. 11, no. 7, pp. 603–617, 2010. View at Publisher · View at Google Scholar · View at Scopus
  112. C. De Wolf, R. Jansen, H. Yamaguchi et al., “Contribution of the drug transporter ABCG2 (breast cancer resistance protein) to resistance against anticancer nucleosides,” Molecular Cancer Therapeutics, vol. 7, no. 9, pp. 3092–3102, 2008. View at Publisher · View at Google Scholar · View at Scopus
  113. J. Yuan, H. Lv, B. Peng, C. Wang, Y. Yu, and Z. He, “Role of BCRP as a biomarker for predicting resistance to 5-fluorouracil in breast cancer,” Cancer Chemotherapy and Pharmacology, vol. 63, no. 6, pp. 1103–1110, 2009. View at Publisher · View at Google Scholar · View at Scopus
  114. M. Ceckova, Z. Vackova, H. Radilova, A. Libra, M. Buncek, and F. Staud, “Effect of ABCG2 on cytotoxicity of platinum drugs: interference of EGFP,” Toxicology in Vitro, vol. 22, no. 8, pp. 1846–1852, 2008. View at Publisher · View at Google Scholar · View at Scopus
  115. E. Herraez, E. Gonzalez-Sanchez, J. Vaquero et al., “Cisplatin-induced chemoresistance in colon cancer cells involves FXR-dependent and FXR-independent up-regulation of ABC proteins,” Molecular Pharmacology, vol. 9, no. 9, pp. 2565–2576, 2012. View at Google Scholar
  116. K. Natarajan, Y. Xie, M. R. Baer, and D. D. Ross, “Role of breast cancer resistance protein (BCRP/ABCG2) in cancer drug resistance,” Biochemical Pharmacology, vol. 83, pp. 1084–1103, 2012. View at Google Scholar
  117. S. Vander Borght, J. Van Pelt, H. Van Malenstein et al., “Up-regulation of breast cancer resistance protein expression in hepatoblastoma following chemotherapy: a study in patients and in vitro,” Hepatology Research, vol. 38, no. 11, pp. 1112–1121, 2008. View at Publisher · View at Google Scholar · View at Scopus
  118. T. Furukawa, M. Komatsu, R. Ikeda, K. Tsujikawa, and S. I. Akiyama, “Copper transport systems are involved in multidrug resistance and drug transport,” Current Medicinal Chemistry, vol. 15, no. 30, pp. 3268–3278, 2008. View at Publisher · View at Google Scholar · View at Scopus
  119. M. Komatsu, T. Sumizawa, M. Mutoh et al., “Copper-transporting P-type adenosine triphosphatase (ATP7B) is associated with cisplatin resistance,” Cancer Research, vol. 60, no. 5, pp. 1312–1316, 2000. View at Google Scholar · View at Scopus
  120. H. Sugeno, Y. Takebayashi, M. Higashimoto et al., “Expression of copper-transporting P-type Adenosine Triphosphatase(ATP7B) in human hepatocellular carcinoma,” Anticancer Research, vol. 24, no. 2, pp. 1045–1048, 2004. View at Google Scholar · View at Scopus
  121. M. Falasca and K. J. Linton, “Investigational ABC transporter inhibitors,” Expert Opinion on Investigational Drugs, vol. 21, pp. 657–666, 2012. View at Google Scholar
  122. S. E. Salmon, W. S. Dalton, T. M. Grogan et al., “Multidrug-resistant myeloma: laboratory and clinical effects of verapamil as a chemosensitizer,” Blood, vol. 78, no. 1, pp. 44–50, 1991. View at Google Scholar · View at Scopus
  123. G. H. Mickisch, M. A. Noordzij, A. V. D. Gaast et al., “Dexverapamil to modulate vinblastine resistance in metastatic renal cell carcinoma,” Journal of Cancer Research and Clinical Oncology, Supplement, vol. 121, no. 3, pp. R11–R16, 1995. View at Google Scholar · View at Scopus
  124. G. Weinländer, G. Kornek, M. Raderer, M. Hejna, C. Tetzner, and W. Scheithauer, “Treatment of advanced colorectal cancer with doxorubicin combined with two potential multidrug-resistance-reversing agents: High-dose oral tamoxifen and dexverapamil,” Journal of Cancer Research and Clinical Oncology, vol. 123, no. 8, pp. 452–455, 1997. View at Publisher · View at Google Scholar · View at Scopus
  125. A. M. Yahanda, K. M. Adler, G. A. Fisher et al., “Phase I trial of etoposide with cyclosporine as a modulator of multidrug resistance,” Journal of Clinical Oncology, vol. 10, no. 10, pp. 1624–1634, 1992. View at Google Scholar · View at Scopus
  126. A. F. List, C. Spier, J. Greer et al., “Phase I/II trial of cyclosporine as a chemotherapy-resistance modifier in acute leukemia,” Journal of Clinical Oncology, vol. 11, no. 9, pp. 1652–1660, 1993. View at Google Scholar · View at Scopus
  127. S. M. Kornblau, E. Estey, T. Madden et al., “Phase I study of mitoxantrone plus etoposide with multidrug blockade by SDZ PSC-833 in relapsed or refractory acute myelogenous leukemia,” Journal of Clinical Oncology, vol. 15, no. 5, pp. 1796–1802, 1997. View at Google Scholar · View at Scopus
  128. J. M. Kovarik, H. S. Purba, M. Pongowski, C. Gerbeau, H. Humbert, and E. A. Mueller, “Pharmacokinetics of dexamethasone and valspodar, a P-glycoprotein (mdr1) modulator: implications for coadministration,” Pharmacotherapy, vol. 18, no. 6 I, pp. 1230–1236, 1998. View at Google Scholar · View at Scopus
  129. M. M. O'Brien, N. J. Lacayo, B. L. Lum et al., “Phase I study of valspodar (PSC-833) with mitoxantrone and etoposide in refractory and relapsed pediatric acute leukemia: a report from the children's oncology group,” Pediatric Blood and Cancer, vol. 54, no. 5, pp. 694–702, 2010. View at Publisher · View at Google Scholar · View at Scopus
  130. C. H. Lee, “Reversing agents for ATP-binding cassette drug transporters,” Methods in Molecular Biology, vol. 596, pp. 325–340, 2010. View at Google Scholar · View at Scopus
  131. R. L. Shepard, J. Cao, J. J. Starling, and A. H. Dantzig, “Modulation of P-glycoprotein but not MRP1- or BCRP-mediated drug resistance by LY335979,” International Journal of Cancer, vol. 103, no. 1, pp. 121–125, 2003. View at Publisher · View at Google Scholar · View at Scopus
  132. D. D. Jandial, S. Farshchi-Heydari, C. A. Larson, G. I. Elliott, W. J. Wrasidlo, and S. B. Howell, “Enhanced delivery of cisplatin to intraperitoneal ovarian carcinomas mediated by the effects of bortezomib on the human copper transporter 1,” Clinical Cancer Research, vol. 15, no. 2, pp. 553–560, 2009. View at Publisher · View at Google Scholar · View at Scopus
  133. Y. K. J. Zhang, R. L. Yeager, and C. D. Klaassen, “Circadian expression profiles of drug-processing genes and transcription factors in mouse liver,” Drug Metabolism and Disposition, vol. 37, no. 1, pp. 106–115, 2009. View at Publisher · View at Google Scholar · View at Scopus
  134. U. P. Zmrzljak and D. Rozman, “Circadian regulation of the hepatic endobiotic and xenobitoic detoxification pathways: the time matters,” Chemical Research in Toxicology, vol. 25, pp. 811–824, 2012. View at Google Scholar