Reversal Agents for Breast Cancer Resistance Protein (BCRP)-Mediated Multidrug Resistance
Jean Boutonnat
Institut Jean Roget, Université Joseph Fourier, Grenoble, France
Hôpital Michallon de Grenoble, Grenoble, France
Search for more papers by this authorAnne Florin
Institut Jean Roget, Université Joseph Fourier, Grenoble, France
Hôpital Michallon de Grenoble, Grenoble, France
Search for more papers by this authorJean Boutonnat
Institut Jean Roget, Université Joseph Fourier, Grenoble, France
Hôpital Michallon de Grenoble, Grenoble, France
Search for more papers by this authorAnne Florin
Institut Jean Roget, Université Joseph Fourier, Grenoble, France
Hôpital Michallon de Grenoble, Grenoble, France
Search for more papers by this authorJean Boutonnat
Institut Jean Roget, Université Joseph Fourier, Grenoble, France
Hôpital Michallon de Grenoble, Grenoble, France
Search for more papers by this authorJacques Robert
Institut Bergonié, Université Victor Segalen, Bordeaux, France
Search for more papers by this authorBinghe Wang
Search for more papers by this authorSummary
This chapter contains sections titled:
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Introduction
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Drugs extruded by BCRP
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Methods to evaluate the activity of BCRP inhibitors
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BCRP inhibitors: Design and activity
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Conclusions and perspectives
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References
REFERENCES
- Doyle LA, Yang W, Abruzzo LV, Krogmann T, Gao Y, Rishi AK et al. 1998. A multidrug resistance transporter from human MCF-7 breast cancer cells. Proc Natl Acad Sci U S A 95: 15665–15670.
- Sarkadi B, Ozvegy-Laczka C, Nemet K, and Varadi A. 2004. ABCG2—A transporter for all seasons. FEBS Lett 567: 116–120.
- Volk EL and Schneider E. 2003. Wild-type breast cancer resistance protein (BCRP/ABCG2) is a methotrexate polyglutamate transporter. Cancer Res 63: 5538–5543.
- Staud F and Pavek P. 2005. Breast cancer resistance protein (BCRP/ABCG2). Int J Biochem Cell Biol 37: 720–725.
- Maliepaard M, van Gastelen MA, Tohgo A, Hausheer FH, van Waardenburg RC, de Jong LA et al. 2001. Circumvention of breast cancer resistance protein (BCRP)-mediated resistance to camptothecins in vitro using non-substrate drugs or the BCRP inhibitor GF120918. Clin Cancer Res 7: 935–941.
- Leslie EM, Deeley RG, and Cole SP. 2005. Multidrug resistance proteins: Role of P-glycoprotein, MRP1, MRP2, and BCRP (ABCG2) in tissue defense. Toxicol Appl Pharmacol 204: 216–237.
- de Vries NA, Zhao J, Kroon E, Buckle T, Beijnen JH, and van Tellingen O. 2007. P-glycoprotein and breast cancer resistance protein: Two dominant transporters working together in limiting the brain penetration of topotecan. Clin Cancer Res 13: 6440–6449.
- Honjo Y, Hrycyna CA, Yan QW, Medina-Perez WY, Robey RW, van de Laar A et al. 2001. Acquired mutations in the MXR/BCRP/ABCP gene alter substrate specificity in MXR/BCRP/ABCP-overexpressing cells. Cancer Res 61: 6635–6639.
- Ross DD, Doyle LA, Yang W, Tong Y, and Cornblatt B. 1995. Susceptibility of idarubicin, daunorubicin, and their C-13 alcohol metabolites to transport-mediated multidrug resistance. Biochem Pharmacol 50: 1673–1683.
- Erlichman C, Boerner SA, Hallgren CG, Spieker R, Wang XY, James CD et al. 2001. The HER tyrosine kinase inhibitor CI1033 enhances cytotoxicity of 7-ethyl-10-hydroxycamptothecin and topotecan by inhibiting breast cancer resistance protein-mediated drug efflux. Cancer Res 61: 739–748.
- Komatani H, Kotani H, Hara Y, Nakagawa R, Matsumoto M, Arakawa H et al. 2001. Identification of breast cancer resistant protein/mitoxantrone resistance/placenta-specific, ATP-binding cassette transporter as a transporter of NB-506 and J-107088, topoisomerase I inhibitors with an indolocarbazole structure. Cancer Res 61: 2827–2832.
- Bates SE, Robey R, Miyake K, Rao K, Ross DD, and Litman T. 2001. The role of half-transporters in multidrug resistance. J Bioenerg Biomembr 33: 503–511.
- Seamon JA, Rugg CA, Emanuel S, Calcagno AM, Ambudkar SV, Middleton SA et al. 2006. Role of the ABCG2 drug transporter in the resistance and oral bio-availability of a potent cyclin-dependent kinase/Aurora kinase inhibitor. Mol Cancer Ther 5: 2459–2467.
- Pan G, Giri N, and Elmquist WF. 2007. Abcg2/Bcrp1 mediates the polarized transport of antiretroviral nucleosides abacavir and zidovudine. Drug Metab Dispos 35: 1165–1173.
- Pavek P, Merino G, Wagenaar E, Bolscher E, Novotna M, Jonker JW et al. 2005. Human breast cancer resistance protein: Interactions with steroid drugs, hormones, the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine, and transport of cimetidine. J Pharmacol Exp Ther 312: 144–152.
- Robey RW, Steadman K, Polgar O, Morisaki K, Blayney M, Mistry P et al. 2004. Pheophorbide a is a specific probe for ABCG2 function and inhibition. Cancer Res 64: 1242–1246.
- Imai Y, Tsukahara S, Ishikawa E, Tsuruo T, and Sugimoto Y. 2002. Estrone and 17-beta-estradiol reverse breast cancer resistance protein-mediated multidrug resistance. Jpn J Cancer Res 93: 231–235.
- Imai Y, Asada S, Tsukahara S, Ishikawa E, Tsuruo T, and Sugimoto Y. 2003. Breast cancer resistance protein exports sulfated estrogens but not free estrogens. Mol Pharmacol 64: 610–618.
- Janvilisri T, Venter H, Shahi S, Reuter G, Balakrishnan L, and van Veen HW. 2003. Sterol transport by the human breast cancer resistance protein (ABCG2) expressed in Lactococcus lactis. J Biol Chem 278: 20645–20651.
- Chen ZS, Guo Y, Belinsky MG, Kotova E, and Kruh GD. 2005. Transport of bile acids, sulfated steroids, estradiol 17-beta-D-glucuronide, and leukotriene C4 by human multidrug resistance protein 8 (ABCC11). Mol Pharmacol 67: 545–557.
- Ifergan I, Jansen G, and Assaraf YG. 2005. Cytoplasmic confinement of breast cancer resistance protein (BCRP/ABCG2) as a novel mechanism of adaptation to short-term folate deprivation. Mol Pharmacol 67: 1349–1359.
- Asashima T, Hori S, Ohtsuki S, Tachikawa M, Watanabe M, Mukai C et al. 2006. ATP-binding cassette transporter G2 mediates the efflux of phototoxins on the luminal membrane of retinal capillary endothelial cells. Pharm Res 23: 1235–1242.
- Vethanayagam RR, Wang H, Gupta A, Zhang Y, Lewis F, Unadkat JD et al. 2005. Functional analysis of the human variants of breast cancer resistance protein: 1206L, N590Y, and D620N. Drug Metab Dispos 33: 697–705.
- Scharenberg CW, Harkey MA, and Torok-Storb B. 2002. The ABCG2 transporter is an efficient Hoechst 33342 efflux pump and is preferentially expressed by immature human hematopoietic progenitors. Blood 99: 507–512.
- Hazlehurst LA, Foley NE, Gleason-Guzman MC, Hacker MP, Cress AE, Greenberger LW et al. 1999. Multiple mechanisms confer drug resistance to mitoxantrone in the human 8226 myeloma cell line. Cancer Res 59: 1021–1028.
- Rabindran SK, Ross DD, Doyle LA, Yang W, and Greenberger LM. 2000. Fumitremorgin C reverses multidrug resistance in cells transfected with the breast cancer resistance protein. Cancer Res 60: 47–50.
- Janvilisri T, Shahi S, Venter H, Balakrishnan L, and van Veen HW. 2005. Arginine-482 is not essential for transport of antibiotics, primary bile acids and unconjugated sterols by the human breast cancer resistance protein (ABCG2). Biochem J 385: 419–426.
- Merlin JL, Bour-Dill C, Marchal S, Ramacci C, Poullain MG, and Giroux B. 2000. Modulation of daunorubicin cellular resistance by combination of P-glycoprotein blockers acting on drug efflux and intracellular drug sequestration in Golgi vesicles. Cytometry 41: 62–72.
- Hendricks CB, Rowinsky EK, Grochow LB, Donehower RC, and Kaufmann SH. 1992. Effect of P-glycoprotein expression on the accumulation and cytotoxicity of topotecan (SK&F 104864), a new camptothecin analogue. Cancer Res 52: 2268–2278.
- Ozvegy-Laczka C, Koblos G, Sarkadi B, and Varadi A. 2005. Single amino acid (482) variants of the ABCG2 multidrug transporter: Major differences in transport capacity and substrate recognition. Biochim Biophys Acta 1668: 53–63.
- Allen JD, van Loevezijn A, Lakhai JM, van der Valk M, van Tellingen O, Reid G et al. 2002. Potent and specific inhibition of the breast cancer resistance protein multidrug transporter in vitro and in mouse intestine by a novel analogue of fumitremorgin C. Mol Cancer Ther 1: 417–425.
- Minderman H, Suvannasankha A, O'Loughlin KL, Scheffer GL, Scheper RJ, Robey RW et al. 2002. Flow cytometric analysis of breast cancer resistance protein expression and function. Cytometry 48: 59–65.
- Jonker JW, Buitelaar M, Wagenaar E, Van Der Valk MA, Scheffer GL, Scheper RJ et al. 2002. The breast cancer resistance protein protects against a major chlorophyll-derived dietary phototoxin and protoporphyria. Proc Natl Acad Sci U S A 99: 15649–15654.
- Litman T, Brangi M, Hudson E, Fetsch P, Abati A, Ross DD et al. 2000. The multidrug-resistant phenotype associated with overexpression of the new ABC half-transporter, MXR (ABCG2). J Cell Sci 113: 2011–2021.
- Houghton PJ, Germain GS, Harwood FC, Schuetz JD, Stewart CF, Buchdunger E et al. 2004. Imatinib mesylate is a potent inhibitor of the ABCG2 (BCRP) transporter and reverses resistance to topotecan and SN-38 in vitro. Cancer Res 64: 2333–2337.
- Minderman H, O'Loughlin KL, Pendyala L, and Baer MR. 2004. VX-710 (biricodar) increases drug retention and enhances chemosensitivity in resistant cells overexpressing P-glycoprotein, multidrug resistance protein, and breast cancer resistance protein. Clin Cancer Res 10: 1826–1834.
- Ozvegy C, Varadi A, and Sarkadi B. 2002. Characterization of drug transport, ATP hydrolysis, and nucleotide trapping by the human ABCG2 multidrug transporter. Modulation of substrate specificity by a point mutation. J Biol Chem 277: 47980–47990.
- Ahmed-Belkacem A, Pozza A, Munoz-Martinez F, Bates SE, Castanys S, Gamarro F et al. 2005. Flavonoid structure-activity studies identify 6-prenylchrysin and tectochrysin as potent and specific inhibitors of breast cancer resistance protein ABCG2. Cancer Res 65: 4852–4860.
- Chu XY, Strauss JR, Mariano MA, Li J, Newton DJ, Cai X et al. 2006. Characterization of mice lacking the multidrug resistance protein MRP2 (ABCC2). J Pharmacol Exp Ther 317: 579–589.
- Alqawi O, Bates S, and Georges E. 2004. Arginine482 to threonine mutation in the breast cancer resistance protein ABCG2 inhibits rhodamine 123 transport while increasing binding. Biochem J 382: 711–716.
- Smith CD, Myers CB, Zilfou JT, Smith SN, and Lawrence DS. 2000. Indoloquinoxaline compounds that selectively antagonize P-glycoprotein. Oncol Res 12: 219–229.
- Xia CQ, Yang JJ, and Gan LS. 2005. Breast cancer resistance protein in pharmacokinetics and drug-drug interactions. Expert Opin Drug Metab Toxicol 1: 595–611.
- Jonker JW, Smit JW, Brinkhuis RF, Maliepaard M, Beijnen JH, Schellens JH et al. 2000. Role of breast cancer resistance protein in the bioavailability and fetal penetration of topotecan. J Natl Cancer Inst 92: 1651–1656.
- Breedveld P, Pluim D, Cipriani G, Wielinga P, van Tellingen O, Schinkel AH et al. 2005. The effect of Bcrp1 (Abcg2) on the in vivo pharmacokinetics and brain penetration of imatinib mesylate (Gleevec): Implications for the use of breast cancer resistance protein and P-glycoprotein inhibitors to enable the brain penetration of imatinib in patients. Cancer Res 65: 2577–2582.
- Cisternino S, Mercier C, Bourasset F, Roux F, and Scherrmann JM. 2004. Expression, up-regulation, and transport activity of the multidrug-resistance protein Abcg2 at the mouse blood-brain barrier. Cancer Res 64: 3296–3301.
- Zaher H, Khan AA, Palandra J, Brayman TG, Yu L, and Ware JA. 2006. Breast cancer resistance protein (Bcrp/abcg2) is a major determinant of sulfasalazine absorption and elimination in the mouse. Mol Pharm 3: 55–61.
- Xia CQ, Liu N, Miwa GT, and Gan LS. 2007. Interactions of cyclosporin A with breast cancer resistance protein. Drug Metab Dispos 35: 576–582.
- Coley HM, Twentyman PR, and Workman P. 1989. Identification of anthracyclines and related agents that retain preferential activity over adriamycin in multidrug-resistant cell lines, and further resistance modification by verapamil and cyclosporin A. Cancer Chemother Pharmacol 24: 284–290.
- Silbermann MH, Boersma AW, Janssen AL, Scheper RJ, Herweijer H, and Nooter K. 1989. Effects of cyclosporin A and verapamil on the intracellular daunorubicin accumulation in Chinese hamster ovary cells with increasing levels of drug-resistance. Int J Cancer 44: 722–726.
- Wierdl M, Wall A, Morton CL, Sampath J, Danks MK, Schuetz JD et al. 2003. Carboxylesterase-mediated sensitization of human tumor cells to CPT-11 cannot override ABCG2-mediated drug resistance. Mol Pharmacol 64: 279–288.
- Ejendal KF and Hrycyna CA. 2005. Differential sensitivities of the human ATP-binding cassette transporters ABCG2 and P-glycoprotein to cyclosporin A. Mol Pharmacol 67: 902–911.
- Qadir M, O'Loughlin KL, Fricke SM, Williamson NA, Greco WR, Minderman H et al. 2005. Cyclosporin A is a broad-spectrum multidrug resistance modulator. Clin Cancer Res 11: 2320–2326.
- Pawarode A, Shukla S, Minderman H, Fricke SM, Pinder EM, O'Loughlin KL et al. 2007. Differential effects of the immunosuppressive agents cyclosporin A, tacrolimus and sirolimus on drug transport by multidrug resistance proteins. Cancer Chemother Pharmacol 60: 179–188.
- Gupta A, Dai Y, Vethanayagam RR, Hebert MF, Thummel KE, Unadkat JD et al. 2006. Cyclosporin A, tacrolimus and sirolimus are potent inhibitors of the human breast cancer resistance protein (ABCG2) and reverse resistance to mitoxantrone and topotecan. Cancer Chemother Pharmacol 58: 374–383.
- Mao Q, Conseil G, Gupta A, Cole SP, and Unadkat JD. 2004. Functional expression of the human breast cancer resistance protein in Pichia pastoris. Biochem Biophys Res Commun 320: 730–737.
- Ozvegy C, Litman T, Szakacs G, Nagy Z, Bates S, Varadi A et al. 2001. Functional characterization of the human multidrug transporter, ABCG2, expressed in insect cells. Biochem Biophys Res Commun 285: 111–117.
- Wang X and Baba M. 2005. The role of breast cancer resistance protein (BCRP/ABCG2) in cellular resistance to HIV-1 nucleoside reverse transcriptase inhibitors. Antivir Chem Chemother 16: 213–216.
- Weiss J, Rose J, Storch CH, Ketabi-Kiyanvash N, Sauer A, Haefeli WE et al. 2007. Modulation of human BCRP (ABCG2) activity by anti-HIV drugs. J Antimicrob Chemother 59: 238–245.
- Ozvegy-Laczka C, Hegedus T, Varady G, Ujhelly O, Schuetz JD, Varadi A et al. 2004. High-affinity interaction of tyrosine kinase inhibitors with the ABCG2 multidrug transporter. Mol Pharmacol 65: 1485–1495.
- Yanase K, Tsukahara S, Asada S, Ishikawa E, Imai Y, and Sugimoto Y. 2004. Gefitinib reverses breast cancer resistance protein-mediated drug resistance. Mol Cancer Ther 3: 1119–1125.
- Burger H, van Tol H, Boersma AW, Brok M, Wiemer EA, Stoter G et al. 2004. Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump. Blood 104: 2940–2942.
- Liu H, Cheng D, Weichel AK, Osipo C, Wing LK, Chen B et al. 2006. Cooperative effect of gefitinib and fumitremorgin C on cell growth and chemosensitivity in estrogen receptor alpha negative fulvestrant-resistant MCF-7 cells. Int J Oncol 29: 1237–1246.
- Cohen JD, Jungheim LN, Muehl BS, and Thrasher KJ. 2002. Preparation of piperidinyl-substituted isoxazolo[4,3-c]quinolinones for inhibiting MRP1. Patent WO 081480, filed 3/27/2002, and issued 10/17/2002.
- Zhang S, Yang X, and Morris ME. 2004. Flavonoids are inhibitors of breast cancer resistance protein (ABCG2)-mediated transport. Mol Pharmacol 65: 1208–1216.
- Zhang S, Yang X, and Morris ME. 2004. Combined effects of multiple flavonoids on breast cancer resistance protein (ABCG2)-mediated transport. Pharm Res 21: 1263–1273.
- Katayama K, Masuyama K, Yoshioka S, Hasegawa H, Mitsuhashi J, and Sugimoto Y. 2007. Flavonoids inhibit breast cancer resistance protein-mediated drug resistance: Transporter specificity and structure-activity relationship. Cancer Chemother Pharmacol 60: 789–797.
- Imai Y, Tsukahara S, Asada S, and Sugimoto Y. 2004. Phytoestrogens/flavonoids reverse breast cancer resistance protein/ABCG2-mediated multidrug resistance. Cancer Res 64: 4346–4352.
- Boumendjel A, Nicolle E, Moraux T, Gerby B, Blanc M, Ronot X et al. 2005. Piperazinobenzopyranones and phenalkylaminobenzopyranones: Potent inhibitors of breast cancer resistance protein (ABCG2). J Med Chem 48: 7275–7281.
- Ahmed-Belkacem A, Macalou S, Borrelli F, Capasso R, Fattorusso E, Taglialatela-Scafati O et al. 2007. Nonprenylated rotenoids, a new class of potent breast cancer resistance protein inhibitors. J Med Chem 50: 1933–1938.
- Dantzig AH, Grese TA, Norman BH, Palkowitz AD, Sluka JP, Starling JJ et al. 1997. Benzothiphene derivatives for treating resistant tumors. Patent EP 773217, filed 11/4/1996, and issued 5/14/1997.
- Hyafil F, Vergely C, Du Vignaud P, and Grand-Perret T. 1993. In vitro and in vivo reversal of multidrug resistance by GF120918, an acridonecarboxamide derivative. Cancer Res 53: 4595–4602.
- de Bruin M, Miyake K, Litman T, Robey R, and Bates SE. 1999. Reversal of resistance by GF120918 in cell lines expressing the ABC half-transporter, MXR. Cancer Lett 146: 117–126.
- Boumendjel A, Macalou S, Ahmed-Belkacem A, Blanc M, and Di Pietro A. 2007. Acridone derivatives: Design, synthesis, and inhibition of breast cancer resistance protein ABCG2. Bioorg Med Chem 15: 2892–2897.
- Rabindran SK, He H, Singh M, Brown E, Collins KI, Annable T et al. 1998. Reversal of a novel multidrug resistance mechanism in human colon carcinoma cells by fumitremorgin C. Cancer Res 58: 5850–5858.
- Robey RW, Medina-Perez WY, Nishiyama K, Lahusen T, Miyake K, Litman T et al. 2001. Overexpression of the ATP-binding cassette half-transporter, ABCG2 (Mxr/BCrp/ABCP1), in flavopiridol-resistant human breast cancer cells. Clin Cancer Res 7: 145–152.
- Usui T, Kondoh M, Cui CB, Mayumi T, and Osada H. 1998. Tryprostatin A, a specific and novel inhibitor of microtubule assembly. Biochem J 333: 543–548.
- Woehlecke H, Osada H, Herrmann A, and Lage H. 2003. Reversal of breast cancer resistance protein-mediated drug resistance by tryprostatin A. Int J Cancer 107: 721–728.
- Brooks TA, Minderman H, O'Loughlin KL, Pera P, Ojima I, Baer MR et al. 2003. Taxane-based reversal agents modulate drug resistance mediated by P-glycoprotein, multidrug resistance protein, and breast cancer resistance protein. Mol Cancer Ther 2: 1195–1205.
- Florin A, Boutonnat J, and Boumendjel A. 2008. Overcoming BCRP-mediated multidrug resistance. Drugs Future 33: 533–540.