S V Ambudkar

Summary

Affiliation: National Institutes of Health
Country: USA

Publications

  1. pmc Sunitinib (Sutent, SU11248), a small-molecule receptor tyrosine kinase inhibitor, blocks function of the ATP-binding cassette (ABC) transporters P-glycoprotein (ABCB1) and ABCG2
    Suneet Shukla
    Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 4256, USA
    Drug Metab Dispos 37:359-65. 2009
  2. ncbi request reprint The power of the pump: mechanisms of action of P-glycoprotein (ABCB1)
    Suresh V Ambudkar
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, DHHS, Bethesda, MD 20892 4256, USA
    Eur J Pharm Sci 27:392-400. 2006
  3. pmc Plasma membrane calcium ATPase (PMCA4): a housekeeper for RT-PCR relative quantification of polytopic membrane proteins
    Anna Maria Calcagno
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, DHHS, Bethesda, MD 20892 42546, USA
    BMC Mol Biol 7:29. 2006
  4. ncbi request reprint P-glycoprotein: from genomics to mechanism
    Suresh V Ambudkar
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute NIH, 37 Convent Drive, Building 37, Room 1A 09, Bethesda, MD 20892 4254, USA
    Oncogene 22:7468-85. 2003
  5. ncbi request reprint The A-loop, a novel conserved aromatic acid subdomain upstream of the Walker A motif in ABC transporters, is critical for ATP binding
    Suresh V Ambudkar
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, DHHS, Bethesda, MD 20892 4256, USA
    FEBS Lett 580:1049-55. 2006
  6. pmc A novel way to spread drug resistance in tumor cells: functional intercellular transfer of P-glycoprotein (ABCB1)
    Suresh V Ambudkar
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 4256, USA
    Trends Pharmacol Sci 26:385-7. 2005
  7. pmc Use of baculovirus BacMam vectors for expression of ABC drug transporters in mammalian cells
    Suneet Shukla
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Drug Metab Dispos 40:304-12. 2012
  8. ncbi request reprint Biochemical, cellular, and pharmacological aspects of the multidrug transporter
    S V Ambudkar
    Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Annu Rev Pharmacol Toxicol 39:361-98. 1999
  9. ncbi request reprint Relation between the turnover number for vinblastine transport and for vinblastine-stimulated ATP hydrolysis by human P-glycoprotein
    S V Ambudkar
    Laboratory of Cell Biology, Division of Basic Sciences, NCI, National Institutes of Health, Bethesda, Maryland 20892 4255, USA
    J Biol Chem 272:21160-6. 1997
  10. ncbi request reprint Functionally similar vanadate-induced 8-azidoadenosine 5'-[alpha-(32)P]Diphosphate-trapped transition state intermediates of human P-glycoprotin are generated in the absence and presence of ATP hydrolysis
    Z E Sauna
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA
    J Biol Chem 276:21199-208. 2001

Collaborators

Detail Information

Publications79

  1. pmc Sunitinib (Sutent, SU11248), a small-molecule receptor tyrosine kinase inhibitor, blocks function of the ATP-binding cassette (ABC) transporters P-glycoprotein (ABCB1) and ABCG2
    Suneet Shukla
    Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 4256, USA
    Drug Metab Dispos 37:359-65. 2009
    ..Taken together, this is the first report showing that sunitinib inhibits transport mediated by ABC drug transporters, which may affect the bioavailability of drugs coadministered with sunitinib...
  2. ncbi request reprint The power of the pump: mechanisms of action of P-glycoprotein (ABCB1)
    Suresh V Ambudkar
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, DHHS, Bethesda, MD 20892 4256, USA
    Eur J Pharm Sci 27:392-400. 2006
    ....
  3. pmc Plasma membrane calcium ATPase (PMCA4): a housekeeper for RT-PCR relative quantification of polytopic membrane proteins
    Anna Maria Calcagno
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, DHHS, Bethesda, MD 20892 42546, USA
    BMC Mol Biol 7:29. 2006
    ....
  4. ncbi request reprint P-glycoprotein: from genomics to mechanism
    Suresh V Ambudkar
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute NIH, 37 Convent Drive, Building 37, Room 1A 09, Bethesda, MD 20892 4254, USA
    Oncogene 22:7468-85. 2003
    ..Understanding of the biology, genetics, and biochemistry of P-gp promises to improve the treatment of cancer and explain the pharmacokinetics of many commonly used drugs...
  5. ncbi request reprint The A-loop, a novel conserved aromatic acid subdomain upstream of the Walker A motif in ABC transporters, is critical for ATP binding
    Suresh V Ambudkar
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, DHHS, Bethesda, MD 20892 4256, USA
    FEBS Lett 580:1049-55. 2006
    ....
  6. pmc A novel way to spread drug resistance in tumor cells: functional intercellular transfer of P-glycoprotein (ABCB1)
    Suresh V Ambudkar
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 4256, USA
    Trends Pharmacol Sci 26:385-7. 2005
    ..Non-genetic transfer of the multidrug resistance phenotype raises fascinating questions about the mechanism and regulation of cell-surface membrane-protein-mediated spread of traits...
  7. pmc Use of baculovirus BacMam vectors for expression of ABC drug transporters in mammalian cells
    Suneet Shukla
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Drug Metab Dispos 40:304-12. 2012
    ..Collectively, these data demonstrate that the BacMam-baculovirus-based expression system can be used to simultaneously study the transport function and biochemical properties of ABC transporters...
  8. ncbi request reprint Biochemical, cellular, and pharmacological aspects of the multidrug transporter
    S V Ambudkar
    Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Annu Rev Pharmacol Toxicol 39:361-98. 1999
    ..This review summarizes current research on the structure-function analysis of P-glycoprotein, its mechanism of action, and facts and speculations about its normal physiological role...
  9. ncbi request reprint Relation between the turnover number for vinblastine transport and for vinblastine-stimulated ATP hydrolysis by human P-glycoprotein
    S V Ambudkar
    Laboratory of Cell Biology, Division of Basic Sciences, NCI, National Institutes of Health, Bethesda, Maryland 20892 4255, USA
    J Biol Chem 272:21160-6. 1997
    ..Thus, ATP hydrolysis is probably directly linked to drug transport by P-glycoprotein...
  10. ncbi request reprint Functionally similar vanadate-induced 8-azidoadenosine 5'-[alpha-(32)P]Diphosphate-trapped transition state intermediates of human P-glycoprotin are generated in the absence and presence of ATP hydrolysis
    Z E Sauna
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA
    J Biol Chem 276:21199-208. 2001
    ..alpha-(32)P]8-azido-ADP (or ADP).Vi transition state complexes generated either in the absence of or accompanying [alpha-(32)P]8-azido-ATP hydrolysis are functionally indistinguishable...
  11. ncbi request reprint Evidence for the vectorial nature of drug (substrate)-stimulated ATP hydrolysis by human P-glycoprotein
    Z E Sauna
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA
    J Biol Chem 276:33301-4. 2001
    ..e. hydrolysis of ATP. These data suggest that substrate-stimulated ATP hydrolysis by Pgp is a vectorial process...
  12. ncbi request reprint Correlation between steady-state ATP hydrolysis and vanadate-induced ADP trapping in Human P-glycoprotein. Evidence for ADP release as the rate-limiting step in the catalytic cycle and its modulation by substrates
    K M Kerr
    Laboratory of Cell Biology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 276:8657-64. 2001
    ..We suggest that substrates modulate the rate of ATPase activity of Pgp by controlling the rate of dissociation of ADP following ATP hydrolysis and that ADP release is the rate-limiting step in the normal catalytic cycle of Pgp...
  13. ncbi request reprint Characterization of the catalytic cycle of ATP hydrolysis by human P-glycoprotein. The two ATP hydrolysis events in a single catalytic cycle are kinetically similar but affect different functional outcomes
    Z E Sauna
    Laboratory of Cell Biology, Division of Basic Sciences, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 276:11653-61. 2001
    ..In aggregate, these findings provide an explanation for the alternate catalysis of ATP hydrolysis and offer a mechanistic framework to elucidate events at both the substrate- and nucleotide-binding sites in the catalytic cycle of Pgp...
  14. ncbi request reprint The molecular basis of the action of disulfiram as a modulator of the multidrug resistance-linked ATP binding cassette transporters MDR1 (ABCB1) and MRP1 (ABCC1)
    Zuben E Sauna
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 4254, USA
    Mol Pharmacol 65:675-84. 2004
    ....
  15. ncbi request reprint Modulation of the function of the multidrug resistance-linked ATP-binding cassette transporter ABCG2 by the cancer chemopreventive agent curcumin
    Wanida Chearwae
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute NIH, Department of Health and Human Services, Bethesda, MD 20892, USA
    Mol Cancer Ther 5:1995-2006. 2006
    ..Collectively, these data show that, among curcuminoids, curcumin I is the most potent modulator of ABCG2 and thus should be considered as a treatment to increase the efficacy of conventional chemotherapeutic drugs...
  16. ncbi request reprint Biochemical basis of polyvalency as a strategy for enhancing the efficacy of P-glycoprotein (ABCB1) modulators: stipiamide homodimers separated with defined-length spacers reverse drug efflux with greater efficacy
    Zuben E Sauna
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892 4254, USA
    Biochemistry 43:2262-71. 2004
    ..These results suggest that polyvalency could be a useful strategy for the development of more potent Pgp modulators...
  17. pmc Curcumin inhibits the activity of ABCG2/BCRP1, a multidrug resistance-linked ABC drug transporter in mice
    Suneet Shukla
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, 20892 4256, USA
    Pharm Res 26:480-7. 2009
    ..To evaluate the in vivo efficacy of curcumin as an inhibitor of the multidrug-resistance-linked ATP Binding Cassette (ABC) drug transporter, ABCG2...
  18. pmc Prolonged drug selection of breast cancer cells and enrichment of cancer stem cell characteristics
    Anna Maria Calcagno
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Natl Cancer Inst 102:1637-52. 2010
    ..We investigated whether prolonged continuous selection of cells for drug resistance enriches cultures for cancer stem-like cells...
  19. ncbi request reprint Multidrug resistance protein 4 (ABCC4)-mediated ATP hydrolysis: effect of transport substrates and characterization of the post-hydrolysis transition state
    Zuben E Sauna
    Laboratory of Cell Biology, Center for Cancer Research, NCI, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892 4256, USA
    J Biol Chem 279:48855-64. 2004
    ....
  20. ncbi request reprint P-glycoprotein and multidrug resistance
    M M Gottesman
    Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Curr Opin Genet Dev 6:610-7. 1996
    ....
  21. pmc Inhibition of P-glycoprotein (ABCB1)- and multidrug resistance-associated protein 1 (ABCC1)-mediated transport by the orally administered inhibitor, CBT-1((R))
    Robert W Robey
    Medical Oncology Branch, Center for Cancer Research, National Institutes of Health, Bethesda, MD 20892, USA
    Biochem Pharmacol 75:1302-12. 2008
    ..CBT-1 is able to inhibit the ABC transporters Pgp and MRP1, making it an attractive candidate for clinical trials in cancers where Pgp and/or MRP1 might be overexpressed. Further clinical studies with CBT-1 are warranted...
  22. ncbi request reprint The calcium channel blockers, 1,4-dihydropyridines, are substrates of the multidrug resistance-linked ABC drug transporter, ABCG2
    Suneet Shukla
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Biochemistry 45:8940-51. 2006
    ....
  23. doi request reprint Development of inhibitors of ATP-binding cassette drug transporters: present status and challenges
    Suneet Shukla
    National Cancer Institute, Laboratory of Cell Biology, Center for Cancer Research, NIH, Bethesda, MD 20892, USA
    Expert Opin Drug Metab Toxicol 4:205-23. 2008
    ..The most recent inhibitors are more potent and less toxic than first-generation compounds, yet some are still prone to adverse effects, poor solubility and unfavorable changes in the pharmacokinetics of the anticancer drugs...
  24. ncbi request reprint The conserved tyrosine residues 401 and 1044 in ATP sites of human P-glycoprotein are critical for ATP binding and hydrolysis: evidence for a conserved subdomain, the A-loop in the ATP-binding cassette
    In Wha Kim
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Biochemistry 45:7605-16. 2006
    ..We named this subdomain the "A-loop" (aromatic residue interacting with the adenine ring of ATP)...
  25. pmc Selective toxicity of NSC73306 in MDR1-positive cells as a new strategy to circumvent multidrug resistance in cancer
    Joseph A Ludwig
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
    Cancer Res 66:4808-15. 2006
    ..This article shows that NSC73306 kills cells with intrinsic or acquired P-gp-induced MDR and indirectly acts to eliminate resistance to MDR1 substrates...
  26. pmc Molecular mechanisms of drug resistance in single-step and multi-step drug-selected cancer cells
    Anna Maria Calcagno
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA
    Methods Mol Biol 596:77-93. 2010
    ..Here, we examine some of the multi-step and single-step selected cell lines generated to elucidate the mechanisms involved in the development of MDR in cancer cells...
  27. ncbi request reprint Genomics and the mechanism of P-glycoprotein (ABCB1)
    Zuben E Sauna
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, DHHS, Building 37, 37 Convent Drive, Bethesda, MD 20892 4256, USA
    J Bioenerg Biomembr 39:481-7. 2007
    ..Our results suggest that the power-stroke is provided only after formation of the pre-hydrolysis transition-like (E.S) state during ATP hydrolysis...
  28. pmc Single-step doxorubicin-selected cancer cells overexpress the ABCG2 drug transporter through epigenetic changes
    A M Calcagno
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, DHHS, Bethesda, MD 20892, USA
    Br J Cancer 98:1515-24. 2008
    ..This is the first report to our knowledge of single-step, low-dose selection leading to overexpression of ABCG2 by epigenetic changes in multiple cancer cell lines...
  29. ncbi request reprint The mechanism of action of multidrug-resistance-linked P-glycoprotein
    Z E Sauna
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
    J Bioenerg Biomembr 33:481-91. 2001
    ....
  30. ncbi request reprint Overview: ABC transporters and human disease
    M M Gottesman
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892 4255, USA
    J Bioenerg Biomembr 33:453-8. 2001
    ..At least 8 members of this family are involved in the transport of a variety of amphipathic compounds, including anticancer drugs, and some appear to contribute to the resistance of cancer cells to chemotherapy...
  31. ncbi request reprint Inhibition of ABCG2-mediated transport by protein kinase inhibitors with a bisindolylmaleimide or indolocarbazole structure
    Robert W Robey
    Medical Oncology Branch and Laboratory of Cell Biology, Center for Cancer Research, NIH, Bethesda, Maryland, USA
    Mol Cancer Ther 6:1877-85. 2007
    ..We find that indolocarbazole and BIM PKIs directly interact with the ABCG2 protein and may thus increase oral bioavailability of ABCG2 substrates...
  32. pmc Evidence for dual mode of action of a thiosemicarbazone, NSC73306: a potent substrate of the multidrug resistance linked ABCG2 transporter
    Chung Pu Wu
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892 4256, USA
    Mol Cancer Ther 6:3287-96. 2007
    ....
  33. ncbi request reprint Importance of the conserved Walker B glutamate residues, 556 and 1201, for the completion of the catalytic cycle of ATP hydrolysis by human P-glycoprotein (ABCB1)
    Zuben E Sauna
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892 4254, USA
    Biochemistry 41:13989-4000. 2002
    ....
  34. ncbi request reprint ABC drug transporters as molecular targets for the prevention of multidrug resistance and drug-drug interactions
    Anna Maria Calcagno
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH DHHS, Bethesda, MD 20892, USA
    Curr Drug Deliv 4:324-33. 2007
    ..Here, we review the current status of methodology used to categorize drug compounds as substrates or modulators for the major ABC drug transporters including ABCB1, ABCC1 and ABCG2...
  35. pmc The naphthoquinones, vitamin K3 and its structural analogue plumbagin, are substrates of the multidrug resistance linked ATP binding cassette drug transporter ABCG2
    Suneet Shukla
    Laboratory of Cell Biology, National Cancer Institute, MSC 4254, 37 Convent Drive, Bethesda, MD 20892 4256, USA
    Mol Cancer Ther 6:3279-86. 2007
    ..Thus, ABCG2 may have a role in the regulation of vitamin K3 levels in the body. In addition, vitamin K3 and its structural derivative, plumbagin, could potentially be used to modulate ABCG2 function...
  36. ncbi request reprint Exploiting reaction intermediates of the ATPase reaction to elucidate the mechanism of transport by P-glycoprotein (ABCB1)
    Zuben E Sauna
    Laboratory of Cell Biology, Center for Cancer Research, NCI, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892 4256, USA
    J Biol Chem 281:26501-11. 2006
    ..This novel approach applies transition state theory to elucidate the mechanism of P-glycoprotein and other ABC transporters and has wider applications in testing cause-effect hypotheses in coupled systems...
  37. pmc Becatecarin (rebeccamycin analog, NSC 655649) is a transport substrate and induces expression of the ATP-binding cassette transporter, ABCG2, in lung carcinoma cells
    Robert W Robey
    Medical Oncology Branch, Center for Cancer Research, National Institutes of Health, Bethesda, MD 20892, USA
    Cancer Chemother Pharmacol 64:575-83. 2009
    ..ABCG2 overexpression has been linked to resistance to topoisomerase inhibitors, leading us to examine the potential interaction between ABCG2 and becatecarin...
  38. ncbi request reprint Comparison of drug transporter levels in normal colon, colon cancer, and Caco-2 cells: impact on drug disposition and discovery
    Anna Maria Calcagno
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Mol Pharm 3:87-93. 2006
    ..However, the molecular "fingerprint" of Caco-2 was distinctly different from tumor samples, indicating that the Caco-2 model would unlikely predict accurate drug absorption for colon cancer sites...
  39. ncbi request reprint Transport activity and surface expression of the Na+-Ca2+ exchanger NCX1 are inhibited by the immunosuppressive agent cyclosporin A and by the nonimmunosuppressive agent PSC833
    Chava Kimchi-Sarfaty
    Laboratory of Cell Biology, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892 4255, USA
    J Biol Chem 277:2505-10. 2002
    ..Furman, I., and Rahamimoff, H. (1999) J. Biol. Chem. 274, 24873-24880) and did not induce its kinesis to the surface membrane, further demonstrating molecular differences between P-glycoprotein and NCX1 mutants for interaction with CsA...
  40. pmc Evaluation of current methods used to analyze the expression profiles of ATP-binding cassette transporters yields an improved drug-discovery database
    Josiah N Orina
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892 4256, USA
    Mol Cancer Ther 8:2057-66. 2009
    ..This study also led to an improved database by revealing previously unidentified substrates for ABCB1, ABCC1, and ABCG2, transporters that contribute to MDR...
  41. pmc Improving cancer chemotherapy with modulators of ABC drug transporters
    S Shukla
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
    Curr Drug Targets 12:621-30. 2011
    ....
  42. ncbi request reprint Mutational analysis of ABCG2: role of the GXXXG motif
    Orsolya Polgar
    Cancer Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland 20892, USA
    Biochemistry 43:9448-56. 2004
    ..These studies support a hypothesis that the GXXXG motif promotes proper packing of the transmembrane segments in the functional ABCG2 homodimer, although it does not solely arbitrate dimerization...
  43. pmc The skin cancer chemotherapeutic agent ingenol-3-angelate (PEP005) is a substrate for the epidermal multidrug transporter (ABCB1) and targets tumor vasculature
    Luowei Li
    Laboratory of Cancer Biology and Genetics, Laboratory of Cell Biology, and Confocal Core Facility, Center for Cancer Research, National Cancer Institute and NIH Chemical Genomics Center, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA
    Cancer Res 70:4509-19. 2010
    ..Taken together, our results suggest that P-gp-mediated absorptive transport, dermal penetration, and vascular damage contribute to the anticancer activity of Ing3A in vivo...
  44. ncbi request reprint About a switch: how P-glycoprotein (ABCB1) harnesses the energy of ATP binding and hydrolysis to do mechanical work
    Zuben E Sauna
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Building 37, Room 2120, 37 Convent Drive, Bethesda, MD 20892 4256, USA
    Mol Cancer Ther 6:13-23. 2007
    ..Based on the mutational and biochemical work on Pgp and structural studies with isolated NBDs, we review proposed schemes for the catalytic cycle of ATP hydrolysis and the transport pathway...
  45. ncbi request reprint A "silent" polymorphism in the MDR1 gene changes substrate specificity
    Chava Kimchi-Sarfaty
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
    Science 315:525-8. 2007
    ....
  46. pmc Mutations define cross-talk between the N-terminal nucleotide-binding domain and transmembrane helix-2 of the yeast multidrug transporter Pdr5: possible conservation of a signaling interface for coupling ATP hydrolysis to drug transport
    Zuben E Sauna
    Laboratory of Cell Biology, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892 4256, USA
    J Biol Chem 283:35010-22. 2008
    ....
  47. pmc Comparison of ATP-binding cassette transporter interactions with the tyrosine kinase inhibitors imatinib, nilotinib, and dasatinib
    Marius Dohse
    Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Drug Metab Dispos 38:1371-80. 2010
    ..Clinical data are required to definitively answer the latter question...
  48. ncbi request reprint Human ABCB6 localizes to both the outer mitochondrial membrane and the plasma membrane
    Jill K Paterson
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, DHHS, Bethesda, Maryland 20892 4256, USA
    Biochemistry 46:9443-52. 2007
    ..These studies are the first to demonstrate that ABCB6 exists in two molecular weight forms, is localized to both the outer mitochondrial membrane and the plasma membrane, and plays a functional role in the plasma membrane...
  49. ncbi request reprint Silent polymorphisms speak: how they affect pharmacogenomics and the treatment of cancer
    Zuben E Sauna
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH and Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA
    Cancer Res 67:9609-12. 2007
    ..We discuss the importance of polymorphisms in drug metabolizing enzymes and transporters in anticancer therapy and suggest that synonymous polymorphisms may play a more significant role than is currently assumed...
  50. pmc Analysis of expression of drug resistance-linked ABC transporters in cancer cells by quantitative RT-PCR
    Anna Maria Calcagno
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA
    Methods Mol Biol 637:121-32. 2010
    ..Gene expression analysis by qRT-PCR is a powerful technique and shows potential as a diagnostic tool for predicting drug response in cancer patients...
  51. ncbi request reprint Catalytic cycle of ATP hydrolysis by P-glycoprotein: evidence for formation of the E.S reaction intermediate with ATP-gamma-S, a nonhydrolyzable analogue of ATP
    Zuben E Sauna
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892 4256, USA
    Biochemistry 46:13787-99. 2007
    ....
  52. pmc Reversal of ABC drug transporter-mediated multidrug resistance in cancer cells: evaluation of current strategies
    Chung Pu Wu
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Curr Mol Pharmacol 1:93-105. 2008
    ..This review summarizes the recent advances in identifying strategies to restore sensitivity to chemotherapeutics in multidrug resistant cancer cells...
  53. doi request reprint The glucose-6-phosphate transporter is a phosphate-linked antiporter deficient in glycogen storage disease type Ib and Ic
    Shih Yin Chen
    Section on Cellular Differentiation, Heritable Disorders Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892 1830, USA
    FASEB J 22:2206-13. 2008
    ..Taken together, our results suggest that G6PT has a dual role as a G6P and a P(i) transporter and that GSD-Ib and GSD-Ic are deficient in the same G6PT gene...
  54. ncbi request reprint Relationship between drugs and functional activity of various mammalian P-glycoproteins (ABCB1)
    In Wha Kim
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Mini Rev Med Chem 8:193-200. 2008
    ..Here, we review differences/similarities in the properties of Pgp from numerous mammalian species commonly used in preclinical studies and discuss their relevance to the pharmacokinetics of potential drug molecules...
  55. pmc Dependence of multidrug resistance protein-mediated cyclic nucleotide efflux on the background sodium conductance
    Marek Kucka
    National Institute of Child Health and Human Development, Bethesda, MD 20892 4510, USA
    Mol Pharmacol 77:270-9. 2010
    ..These results indicate that the MRP4/5-mediated cyclic nucleotide efflux can be rapidly modulated by membrane potential determined by the background Na(+) conductance...
  56. ncbi request reprint Elf1p, a member of the ABC class of ATPases, functions as a mRNA export factor in Schizosacchromyces pombe
    Libor Kozak
    Basic Research Laboratory, Center for Cancer Research, NCI National Institutes of Health, Bldg 37 Rm 6138B, 9000 Rockville Pike, Bethesda, MD 20892, USA
    J Biol Chem 277:33580-9. 2002
    ..This mutant protein no longer functions in mRNA export. Taken together, our results show that Elf1p functions as a mRNA export factor along with Rae1p and Mex67p in S. pombe...
  57. ncbi request reprint Disulfiram, an old drug with new potential therapeutic uses for human cancers and fungal infections
    Zuben E Sauna
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, DHHS, Bethesda, Maryland 20892 4256, USA
    Mol Biosyst 1:127-34. 2005
    ..This review discusses the molecular mechanism of action of disulfiram and its potential use in the treatment of human cancers and fungal infections...
  58. ncbi request reprint Disulfiram is a potent modulator of multidrug transporter Cdr1p of Candida albicans
    Suneet Shukla
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 4256, USA
    Biochem Biophys Res Commun 322:520-5. 2004
    ..Collectively these results demonstrate that disulfiram reverses Cdr1p-mediated drug resistance by interaction with both ATP and substrate-binding sites of the transporter and may be useful for antifungal therapy...
  59. pmc Discovering natural product modulators to overcome multidrug resistance in cancer chemotherapy
    Chung Pu Wu
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA
    Curr Pharm Biotechnol 12:609-20. 2011
    ..Here, we present a brief overview of the prospect of using natural products to modulate the function of ABC drug transporters clinically and their impact on human physiology and pharmacology...
  60. pmc Brca1 breast tumors contain distinct CD44+/CD24- and CD133+ cells with cancer stem cell characteristics
    Mollie H Wright
    Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, 9000 Rockville Pike, Bethesda, Maryland 20892, USA
    Breast Cancer Res 10:R10. 2008
    ..Whether cancer stem cells occur in BRCA1-associated breast cancer and contribute to therapeutic response is not known...
  61. ncbi request reprint Evidence for the role of glycosylation in accessibility of the extracellular domains of human MRP1 (ABCC1)
    Marianna Müller
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive MSC 4254, Bethesda, MD 20892 4254, USA
    Biochemistry 41:10123-32. 2002
    ....
  62. ncbi request reprint VAMP2-dependent exocytosis regulates plasma membrane insertion of TRPC3 channels and contributes to agonist-stimulated Ca2+ influx
    Brij B Singh
    Secretory Physiology Section, Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, Bethesda, MD 20892, USA
    Mol Cell 15:635-46. 2004
    ..In aggregate, these data suggest that VAMP2-dependent exocytosis regulates plasma membrane insertion of TRPC3 channels and contributes to carbachol-stimulation of Ca2+ influx...
  63. ncbi request reprint Nonequivalence of the nucleotide binding domains of the ArsA ATPase
    Yong Jiang
    Department of Biochemistry and Molecular Biology, Wayne State University, School of Medicine, 540 E Canfield Ave, Detroit, Michigan 48201, USA
    J Biol Chem 280:9921-6. 2005
    ..These results suggest that the two homologous halves of the ArsA may be functionally nonequivalent...
  64. ncbi request reprint The role of hydrogen bond acceptor groups in the interaction of substrates with Pdr5p, a major yeast drug transporter
    Leanne Hanson
    Department of Biology, The Catholic University of America, Washington, DC 20064, USA
    Biochemistry 44:9703-13. 2005
    ..The presence of multiple sites with different requirements for substrate-Pdr5p interaction may explain the broad specificity of xenobiotic compounds transported by this protein...
  65. pmc Functional characterization of Candida albicans ABC transporter Cdr1p
    Suneet Shukla
    Membrane Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India
    Eukaryot Cell 2:1361-75. 2003
    ....
  66. pmc New inhibitors of ABCG2 identified by high-throughput screening
    Curtis J Henrich
    Basic Research Program, Science Applications International Corporation Frederick, Inc, Building 560, Room 32 63A, NCI Frederick, Frederick, MD 21702, USA
    Mol Cancer Ther 6:3271-8. 2007
    ..These five novel inhibitors of ABCG2 activity may provide a basis for further investigation of ABCG2 function and its relevance in multidrug resistance...
  67. ncbi request reprint Curcuminoids purified from turmeric powder modulate the function of human multidrug resistance protein 1 (ABCC1)
    Wanida Chearwae
    Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Thailand
    Cancer Chemother Pharmacol 57:376-88. 2006
    ..In summary, these results demonstrate that curcuminoids effectively inhibit MRP1-mediated transport and among curcuminoids, curcumin I, a major constituent of curcumin mixture, is the best modulator...
  68. ncbi request reprint Modulation of function of three ABC drug transporters, P-glycoprotein (ABCB1), mitoxantrone resistance protein (ABCG2) and multidrug resistance protein 1 (ABCC1) by tetrahydrocurcumin, a major metabolite of curcumin
    Pornngarm Limtrakul
    Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
    Mol Cell Biochem 296:85-95. 2007
    ..Taken together, this study clearly showed that THC inhibits the efflux function of P-gp, MXR and MRP1 and it is able to extend the MDR reversing activity of curcuminoids in vivo...
  69. ncbi request reprint Modulation of P-glycoprotein expression and function by curcumin in multidrug-resistant human KB cells
    Songyot Anuchapreeda
    Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Thailand 50200
    Biochem Pharmacol 64:573-82. 2002
    ..In summary, this study describes the duel modulation of MDR1 expression and Pgp function by the phytochemical curcumin, which may be an attractive new agent for the chemosensitization of cancer cells...
  70. ncbi request reprint Differential effects of the immunosuppressive agents cyclosporin A, tacrolimus and sirolimus on drug transport by multidrug resistance proteins
    Attaphol Pawarode
    Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA
    Cancer Chemother Pharmacol 60:179-88. 2007
    ....
  71. ncbi request reprint Erlotinib (Tarceva, OSI-774) antagonizes ATP-binding cassette subfamily B member 1 and ATP-binding cassette subfamily G member 2-mediated drug resistance
    Zhi Shi
    Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, St John s University, Jamaica, New York 11439, USA
    Cancer Res 67:11012-20. 2007
    ..These findings may be useful for cancer combinational therapy with erlotinib in the clinic...
  72. ncbi request reprint Role of the ABCG2 drug transporter in the resistance and oral bioavailability of a potent cyclin-dependent kinase/Aurora kinase inhibitor
    Jennifer A Seamon
    Cancer Therapeutics Research, Johnson and Johnson Pharmaceutical Research and Development, LLC, Raritan, NJ 08560, USA
    Mol Cancer Ther 5:2459-67. 2006
    ..These findings indicate that ABCG2 mediates the resistance to JNJ-7706621 and alters the absorption of the compound following administration...
  73. ncbi request reprint The yeast Pdr5p multidrug transporter: how does it recognize so many substrates?
    John Golin
    Department of Biology, The Catholic University of America, Washington, DC 20064, USA
    Biochem Biophys Res Commun 356:1-5. 2007
    ..All Pdr5p substrates, however, have a size requirement that is independent of hydrophobicity...
  74. ncbi request reprint Sipholenol A, a marine-derived sipholane triterpene, potently reverses P-glycoprotein (ABCB1)-mediated multidrug resistance in cancer cells
    Zhi Shi
    Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, St John s University, Jamaica, NY 11439, USA
    Cancer Sci 98:1373-80. 2007
    ....
  75. ncbi request reprint Complete inhibition of the Pdr5p multidrug efflux pump ATPase activity by its transport substrate clotrimazole suggests that GTP as well as ATP may be used as an energy source
    John Golin
    Department of Biology, The Catholic University of America, Washington, DC 20064, USA
    Biochemistry 46:13109-19. 2007
    ..We propose that Pdr5p increases its multidrug transport substrate specificity by using more than one nucleotide as an energy source...
  76. pmc Interactions of mefloquine with ABC proteins, MRP1 (ABCC1) and MRP4 (ABCC4) that are present in human red cell membranes
    Chung Pu Wu
    Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QJ, UK
    Biochem Pharmacol 70:500-10. 2005
    ..But at concentrations achieved clinically mefloquine is unlikely to affect the MRP1-mediated transport of GSSG across the erythrocyte membrane...
  77. pmc Modulatory effects of plant phenols on human multidrug-resistance proteins 1, 4 and 5 (ABCC1, 4 and 5)
    Chung Pu Wu
    Department of Pharmacology, University of Cambridge, UK
    FEBS J 272:4725-40. 2005
    ..Such interactions could influence bioavailability of anticancer and antiviral drugs in vivo and thus, should be considered for increasing efficacy in drug therapies...
  78. ncbi request reprint Studies with novel Pdr5p substrates demonstrate a strong size dependence for xenobiotic efflux
    John Golin
    Department of Biology and Chemistry, Catholic University of America, Washington, DC 20064, USA
    J Biol Chem 278:5963-9. 2003
    ..The surprising observation that Pdr5p mediates resistance to tetraalkyltins suggests that one of the sites might use only hydrophobic interactions to bind substrates...
  79. pmc Conserved Asp327 of walker B motif in the N-terminal nucleotide binding domain (NBD-1) of Cdr1p of Candida albicans has acquired a new role in ATP hydrolysis
    Versha Rai
    Membrane Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India
    Biochemistry 45:14726-39. 2006
    ....