Abstract
The gene family of ATP-binding cassette (ABC) transporters is widely distributed over the evolutionary tree of life from bacteria to man. In cancer, several ABC transporters are involved in the transport of anticancer drugs. This leads to the development of resistance to a broad spectrum of anticancer agents, termed multidrug resistance. An attractive strategy to overcome multidrug resistance is to block the transport function of ABC transporters leading to lethal intracellular concentrations of anticancer drugs. Efforts to identify transport inhibitors lead to a huge amount of chemical substances, none of which successfully passed clinical trials in cancer patients because of high toxicity. The search of natural products from traditional Chinese medicine may be more promising because natural products frequently are less toxic than chemically synthesized xenobiotics. Here, we give an overview of ABC transporters involved in multidrug resistance of cancer as well as Chinese herbs and phytochemicals showing inhibitory activity towards ABC transporters.
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References
Abidi P, Chen W, Kraemer FB, Li H, Liu J (2006) The medicinal plant goldenseal is a natural LDL-lowering agent with multiple bioactive components and new action mechanisms. J Lipid Res 47:2134–2147
Adams M, Mahringer A, Kunert O, Fricker G, Efferth T, Bauer R (2007a) Cytotoxicity and p-glycoprotein modulating effects of quinolones and indoloquinazolines from the Chinese herb Evodia rutaecarpa. Planta Med 73:1554–1557
Adams M, Mahringer A, Bauer R, Fricker G, Efferth T (2007b) In vitro cytotoxicity and P-glycoprotein modulating effects of geranylated furocoumarins from Tetradium daniellii. Planta Med 73:1475–1478
Allen SS, Cutting GR, Guggino WB (1995) CFTR regulates outwardly rectifying chloride channels through an autocrine mechanism involving ATP. Cell 81:1063–1073
Allen JD, Brinkhuis RF, Wijnholds J, Schinkel AH (1999) The mouse Bcrp1/Mxr/Abcp gene: amplification and overexpression in cell lines selected for resistance to topotecan, mitoxantrone, or doxorubicin. Cancer Res 59:4237–4241
Aller SG, Yu J, Ward A, Weng Y, Chittaboina S, Zhuo R, Harrell PM, Trinh YT, Zhang Q, Urbatsch IL, Chang G (2009) Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding. Science 323:1718–1722
Allikmets R, Schrime LM, Hutchinson A, Romano-Spica V, Dean M (1998a) A human placenta-specific ATP-binding cassette gene (ABCP) on chromosome 4q22 that is involved in multidrug resistance. Cancer Res 58:5337–5339
Allikmets R, Schriml LM, Hutchinson A, Romano-Spica V, Dean M (1998b) A human placenta-specific ATP-binding cassette gene (ABCP) on chromosome 4q22 that is involved in multidrug resistance. Cancer Res 58:5337–5339
Angelini A, Di Ilio C, Castellani ML, Conti P, Cuccurullo F (2010) Modulation of multidrug resistance p-glycoprotein activity by flavonoids and honokiol in human doxorubicin- resistant sarcoma cells (MES-SA/DX-5): implications for natural sedatives as chemosensitizing agents in cancer therapy. J Biol Regul Homeost Agents 24:197–205
Arai Y, Masuda M, Sugawara I, Arai T, Motoji T, Tsuruo T, Oshimi K, Mizoguchi HY (1997) Expression of the MDR1 and MDR3 gene products in acute and chronic leukemias. Leuk Res 21:313–319
Baer MR, George SL, Dodge RK (2002) Phase 3 study of the multidrug-resistance modulator PSC-833 in previously untreated patients 60 years of age and older with acute myeloid leukemia: Cancer and Leukemia Group B Study 9720. Blood 100:1224–1232
Bansal T, Awasthi A, Jaggi M, Khar RK, Talegaonkar S (2008) Pre-clinical evidence for altered absorption and biliary excretion of irinotecan (CPT-11) in combination with quercetin: possible contribution of P-glycoprotein. Life Sci 83:250–259
Bates SE, Robey R, Miyake K, Rao K, Ross DD, Litman T (2001) The role of half-transporters in multidrug resistance. J Bioenerg Biomembr 33:503–511
Belinsky MG, Chen ZS, Shchaveleva I, Zeng H, Kruh GD (2002) Characterization of the drug resistance and transport properties of multidrug resistance protein 6 (MRP6, ABCC6). Cancer Res 62:6172–6177
Bera TK, Lee S, Salvatore G, Lee B, Pastan I (2001) MRP8, a new member of ABC transporter superfamily, identified by EST database mining and gene prediction program, is highly expressed in breast cancer. Mol Med 7:509–516
Bera TK, Iavarone C, Kumar V, Lee S, Lee B, Pastan I (2002) MRP9, an unusual truncated member of the ABC transporter superfamily, is highly expressed in breast cancer. Proc Natl Acad Sci USA 99:6997–7002
Bergen AAB, Plomp AS, Schuurman EJ, Terry S, Breuning M, Dauwerse H, Swart J, Kool M, van Soest S, Baas F, ten Brink JB, de Jong PT (2000) Mutations in ABCC6 cause pseudoxanthoma elasticum. Nat Genet 25:228–231
Bieche I, Girault I, Urbain E, Tozlu S, Lidereau R (2004) Relationship between intratumoral expression of genes coding for xenobioticmetabolizing enzymes and benefit from adjuvant tamoxifen in estrogen receptor alpha-positive postmenopausal breast carcinoma. Breast Cancer Res 6:R252–R263
Boonstra R, Timmer-Bosscha H, van Echten-Arends J, van der Kolk DM, van den Berg A, de Jong B, Tew KD, Poppema S, de Vries EG (2004) Mitoxantrone resistance in a small cell lung cancer cell line is associated with ABCA2 upregulation. Br J Cancer 90:2411–2417
Borst P, Evers R, Kool M, Wijnholds J (1999) The multidrug resistance protein family. Biochim Biophys Acta 1461:347–357
Brand W, van der Wel PA, Rein MJ, Barron D, Williamson G, van Bladeren PJ, Rietjens IM (2008) Metabolism and transport of the citrus flavonoid hesperetin in Caco-2 cell monolayers. Drug Metab Dispos 36:1794–1802
Büchler M, König J, Brom M, Kartenbeck J, Spring H, Horie T, Keppler D (1996) cDNA cloning of the hepatocyte canalicular isoform of the multidrug resistance protein, cMrp, reveals a novel conjugate export pump deficient in hyperbilirubinemic mutant rats. J Biol Chem 271:15091–15098
Calcabrini A, Stringaro A, Toccacieli L, Meschini S, Marra M, Colone M, Salvatore G, Mondello F, Arancia G, Molinari A (2004) Terpinen-4-ol, the main component of Melaleuca alternifolia (tea tree) oil inhibits the in vitro growth of human melanoma cells. J Invest Dermatol 122:349–360
Cao J, Chen X, Liang J, Yu XQ, Xu AL, Chan E, Wei D, Huang M, Wen JY, Yu XY, Li XT, Sheu FS, Zhou SF (2007) Role of P-glycoprotein in the intestinal absorption of glabridin, an active flavonoid from the root of Glycyrrhiza glabra. Drug Metab Dispos 35:539–553
Carr IB (1987) Pleiotropic drug resistance in hepatocytes induced by carcinogens administered to rats. Cancer Res 47:5577–5583
Chan K, Liu ZQ, Jiang ZH, Zhou H, Wong YF, Xu HX, Liu L (2006) The effects of sinomenine on intestinal absorption of paeoniflorin by the everted rat gut sac model. J Ethnopharmacol 103:425–432
Chang JY, Chang CY, Kuo CC, Chen LT, Wein YS, Kuo YH (2004) Salvinal, a novel microtubule inhibitor isolated from Salvia miltiorrhizae Bunge (Danshen), with antimitotic activity in multidrug-sensitive and -resistant human tumor cells. Mol Pharmacol 65:77–84
Chapman RS, Whetton AD, Dive C (1994) The suppression of drug-induced apoptosis by activation of v-ABL protein tyrosine kinase. Cancer Res 54:5131–5137
Chearwae W, Wu CP, Chu HY, Lee TR, Ambudkar SV, Limtrakul P (2006) Curcuminoids purified from turmeric powder modulate the function of human multidrug resistance protein 1 (ABCC1). Cancer Chemother Pharmacol 57:376–388
Chen CJ, Chin JE, Ueda K, Clark DP, Pastan I, Gottesman MM, Roninson IB (1986) Internal duplication and homology with bacterial transport proteins in the mdr1 (P-glycoprotein) gene from multidrug-resistant human cells. Cell 47:381–389
Chen ZS, Lee K, Kruh GD (2001) Transport of cyclic nucleotides and estradiol 17-beta-D-glucuronide by multidrug resistance protein 4. Resistance to 6-mercaptopurine and 6-thioguanine. J Biol Chem 276:33747–33754
Chen HY, Wu TS, Su SF, Kuo SC, Chao PD (2002) Marked decrease of cyclosporin absorption caused by phellamurin in rats. Planta Med 68:138–141
Chen KG, Valencia JC, Lai B, Zhang G, Paterson JK, Rouzaud F, Berens W, Wincovitch SM, Garfield SH, Leapman RD, Hearing VJ, Gottesman MM (2006) Melanosomal sequestration of cytotoxic drugs contributes to the intractability of malignant melanomas. Proc Natl Acad Sci USA 103:9903–9907
Chen Y, Wang X, Sun H, Xing D, Hu J, Wai Z, Du L (2008a) Characterization of the transportation of berberine in Coptidis rhizoma extract through rat primary cultured cortical neurons. Biomed Chromatogr 22:28–33
Chen Y, Zhao YH, Jia XB, Hu M (2008b) Intestinal absorption mechanisms of prenylated flavonoids present in the heat-processed Epimedium koreanum Nakai (Yin Yanghuo). Pharm Res 25:2190–2199
Chen YW, Lin GJ, Chuang YP, Chia WT, Hueng DY, Lin CK, Nieh S, Sytwu HK (2010) Triptolide circumvents drug-resistant effect and enhances 5-fluorouracil antitumor effect on KB cells. Anticancer Drugs 21:502–513
Childs S, Yeh RL, Georges E, Ling VS, Childs RL, Yeh E, Georges VL (1995) Identification of a sister gene to P-glycoprotein. Cancer Res 55:2029–2034
Childs S, Yeh RL, Hui D, Ling V (1998) Taxol resistance mediated by transfection of the liver-specific sister gene of P-glycoprotein. Cancer Res 58:4160–4167
Choi KH, Chen CJ, Kriegler M, Roninson IB (1988) An altered pattern of cross-resistance in multidrug-resistant human cells results from spontaneous mutations in the mdr1 (P-glycoprotein) gene. Cell 53:519–529
Choi SU, Park SH, Kim KH, Choi EJ, Kim S, Park WK, Zhang YH, Kim HS, Jung NP, Lee CO (1998) The bisbenzylisoquinoline alkaloids, tetrandine and fangchinoline, enhance the cytotoxicity of multidrug resistance-related drugs via modulation of P-glycoprotein. Anticancer Drugs 9:255–261
Choi CH, Kang G, Min YD (2003) Reversal of P-glycoprotein-mediated multidrug resistance by protopanaxatriol ginsenosides from Korean red ginseng. Planta Med 69:235–240
Cole SP, Deeley RG (1998) Multidrug resistance mediated by the ATP-binding cassette transporter protein MRP. Bioessays 20:931–940
Cole SP, Bhardwaj G, Gerlach JH, Mackie JE, Grant CE, Almquist KC, Stewart AJ, Kurz EU, Duncan AM, Deeley RG (1992) Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. Science 258:1650–1654
Cole SPC, Sparks KE, Fraser K, Loe DW, Grant CE, Wilson GM, Deeley DR (1994) Pharmacological characterization of multidrug resistant MRP-transfected human tumor cells. Cancer Res 54:5902–5910
Cui Y, König J, Buchholz U, Spring H, Leier I, Keppler D (1999) Drug resistance and ATP-dependent conjugate transport mediated by the apical multidrug resistance protein, MRP2, permanently expressed in human and canine cells. Mol Pharmacol 55:929–937
Dai JY, Yang JL, Li C (2008) Transport and metabolism of flavonoids from Chinese herbal remedy Xiaochaihu- tang across human intestinal Caco-2 cell monolayers. Acta Pharmacol Sin 29:1086–1093
Dalton WS, Crowley JJ, Salmon SS, Grogan TM, Laufman LR, Weiss GR, Bonnet JD (1995) A phase II randomized study of oral verapamil as a chemosensitizer to reverse drug resistance in patients with refractory myeloma. A Southwest Oncology Group study. Cancer 75:815–820
Dean M, Allikmets R (1995) Evolution of ATP-binding cassette transporter genes. Curr Opin Genet Dev 5:779–785
Dong Y, Zhang Y, Yang Q, Li Y, Zhu X (2009) Absorption of extractive Radix Paeoniae Alba in rat everted gut sacs and its interaction with P-glycoprotein [Article in Chinese]. Zhongguo Zhong Yao Za Zhi 34:884–888
Doyle LA, Ross DD (2003) Multidrug resistance mediated by the breast cancer resistance protein BCRP (ABCG2). Oncogene 22:7340–7358
Doyle LA, Yang W, Abruzzo LV, Krogmann T, Gao Y, Rishi AK, Ross DD (1998) A multidrug resistance transporter from human MCF-7 breast cancer cells. Proc Natl Acad Sci USA 95:15665–15670
Ebert B, Seidel A, Lampen A (2007) Phytochemicals induce breast cancer resistance protein in Caco-2 cells and enhance the transport of benzo[a]pyrene-3-sulfate. Toxicol Sci 96:227–236
Efferth T (1997) Die Zellbiologie der Tumorresistenz: Multidrug-Resistenz, genspezifische DNS-Schädigung und Apoptose. Habilitationsschrift, Aachen
Efferth T, Grassmann R (2000) Impact of viral oncogenesis on responses to anti-cancer drugs and irradiation. Crit Rev Oncog 11:165–187
Efferth T, Volm M (1993a) Modulation of P-glycoprotein-mediated multidrug resistance by monoclonal antibodies, immunotoxins or antisense oligodeoxynucleotides in kidney carcinoma and normal kidney cells. Oncology 50:303–308
Efferth T, Volm M (1993b) Reversal of doxorubicin-resistance in sarcoma 180 tumor cells by inhibition of different resistance mechanisms. Cancer Lett 70:197–202
Efferth T, Klett T, Mattern J, Osswald H, Pommerenke EW, Stöhr M, Volm M (1991) Reversing multidrug resistance in L1210 tumor cells by hycanthone or chlorophenoxamine in vitro and in vivo. Anticancer Res 11:1275–1279
Efferth T, Dunn TA, Berlion M, Langenbahn H, Pommerenke EW, Volm M (1993) Reversal of inherent multidrug-resistance in primary human renal cell carcinoma cell cultures by S 9788. Anticancer Res 13:905–908
Efferth T, Davey M, Olbrich A, Rücker G, Gebhart E, Davey R (2002) Activity of drugs from traditional Chinese medicine toward sensitive and MDR1- or MRP1-overexpressing multidrug-resistant human CCRF-CEM leukemia cells. Blood Cells Mol Dis 28:160–168
Efferth T, Gillet JP, Sauerbrey A, Zintl F, Bertholet V, de Longueville F, Remacle J, Steinbach D (2006) Expression profiling of ATP binding cassette transporters in childhood T-cell acute lymphoblastic leukemia. Mol Cancer Ther 5:1986–1994
Efferth T, Li PC, Konkimalla VS, Kaina B (2007) From traditional Chinese medicine to rational cancer therapy. Trends Mol Med 13:353–361
Efferth T, Konkimalla VB, Wang YF, Sauerbrey A, Meinhardt S, Zintl F, Mattern J, Volm M (2008) Prediction of broad spectrum resistance of tumors towards anticancer drugs. Clin Cancer Res 14:2405–2412
Eichhorn T, Efferth T (2012) P-glycoprotein and its inhibition in tumors by phytochemicals derived from Chinese herbs. J Ethnopharmacol 141:557–70
Eswar N, Webb B, Marti-Renom MA, Madhusudhan MS, Eramian D, Shen MY, Pieper U, Sali A (2006) Comparative protein structure modeling using modeller. Curr Protoc Bioinformatics Chapter 5: Unit 5.6
Evers R, Cnubben NHP, Wijnholds J, van Deemter L, van Bladeren PJ, Borst P (1997) Transport of glutathione prostaglandin A conjugates by the multidrug resistance protein 1. FEBS Lett 419:112–116
Evers R, Kool M, van Deemter L, Janssen H, Caolafat J, Oomen LC, Paulusma CC, Oude Elferink RP, Baas F, Schinkel AH, Borst P (1998) Drug export activity of the human canalicular multispecific organic anion transporter in polarized kidney MDCK cells expressing cMOAT (MRP2) cDNA. J Clin Invest 101:1310–1319
Fairchild CR, Ivy SP, Rushmore T, Lee G, Koo P, Goldsmith M, Myers CE, Farber E, Cowan KH (1987) Carcinogen-induced mdr overexpression is associated with xenobiotic resistance in rat preneoplastic liver nodules and hepatocellular carcinomas. Proc Natl Acad Sci USA 84:7701–7705
Fan L, Tao GY, Wang G, Chen Y, Zhang W, He YJ, Li Q, Lei HP, Jiang F, Hu DL, Huang YF, Zhou HH (2009a) Effects of Ginkgo biloba extract ingestion on the pharmacokinetics of talinolol in healthy Chinese volunteers. Ann Pharmacother 43:944–949
Fan L, Mao XQ, Tao GY, Wang G, Jiang F, Chen Y, Li Q, Zhang W, Lei HP, Hu DL, Huang YF, Wang D, Zhou HH (2009b) Effect of Schisandra chinensis extract and Ginkgo biloba extract on the pharmacokinetics of talinolol in healthy volunteers. Xenobiotica 39:249–254
Farabegoli F, Papi A, Bartolini G, Ostan R, Orlandi M (2010) (−)-Epigallocatechin-3-gallate downregulates Pg-P and BCRP in a tamoxifen resistant MCF-7 cell line. Phytomedicine 17:356–362
Fellner S, Bauer B, Miller DS, Schaffrik M, Fankhanel M, Spruss T, Bernhardt G, Graeff C, Farber L, Gschaidmeier H, Buschauer A, Fricker G (2002) Transport of paclitaxel (Taxol) across the blood–brain barrier in vitro and in vivo. J Clin Invest 110:1309–1318
Fernandez-Checa JC, Takikawa H, Horie T, Ookhtens M, Kaplowitz N (1992) Canalicular transport of reduced glutathione in normal and mutant Eisai hyperbilirubinemic rats. J Biol Chem 267:1667–1673
Fischer V, Rodriguez-Gascon A, Heitz F, Tynes R, Hauck C, Cohen D, Vickers AE (1998) The multidrug resistance modulator valspodar (PSC 833) is metabolized by human cytochrome P450 3A. Implications for drug–drug interactions and pharmacological activity of the main metabolite. Drug Metab Dispos 26:802–811
Fong WF, Wan CK, Zhu GY, Chattopadhyay A, Dey S, Zhao Z, Shen XL (2007a) Schisandrol A from Schisandra chinensis reverses P-glycoprotein-mediated multidrug resistance by affecting Pgp-substrate complexes. Planta Med 73:212–220
Fong WF, Wang C, Zhu GY, Leung CH, Yang MS, Cheung HY (2007b) Reversal of multidrug resistance in cancer cells by Rhizoma Alismatis extract. Phytomedicine 14:160–165
Ford JM, Hait WN (1993) Pharmacologic circumvention of multidrug resistance. Cytotechnology 12:171–212
Fracasso PM, Goldstein LJ, de Alwis DP, Rader JS, Arquette MA, Goodner SA, Wright LP, Fears CL, Gazak RJ, Andre VA, Burgess MF, Slapak CA, Schellens JH (2004) Phase I study of docetaxel in combination with the P-glycoprotein inhibitor, zosuquidar, in resistant malignancies. Clin Cancer Res 10:7220–7228
Frank NY, Margaryan A, Huang Y, Schatton T, Waaga-Gasser AM, Gasser M, Sayegh MH, Sadee W, Frank MH (2005) ABCB5-mediated doxorubicin transport and chemoresistance in human malignant melanoma. Cancer Res 65:4320–4333
Fu LW, He LR, Liang YJ, Chen LM, Xiong HY, Yang XP, Pan QC (2003) Experimental chemotherapy against xenografts derived from multidrug resistant KBv200 cells and parental drug-sensitive KB cells in nude mice by annonaceous acetogenin 89–2. Yao Xue Xue Bao 38:565–570
Gao N, Zhang Y, Mao JQ, Li GQ, Zhou W, Gao B, Gu J (2008) Effects of some traditional Chinese drugs on Mdr1 gene and its expression product in K562/A02 cells [Article in Chinese]. Zhongguo Shi Yan Xue Ye Xue Za Zhi 16:785–789
Geng J, Zhou D (2008) Coriaria lactone induces in vitro the overexpression of multidrug resistance P-glycoprotein in astrocyte from rat brain [Article in Chinese]. Sichuan Da Xue Xue Bao Yi Xue Ban 39:80–83
Gerloff T, Steiger B, Hagenbuch B, Madon J, Landmann L, Roth J, Hofmann AF, Meier PJ (1998) The sister of P-glycoprotein represents the canalicular bile salt export pump of mammalian liver. J Biol Chem 273:10046–10050
Gillet JP, Schneider J, Bertholet V, de Longueville F, Remacle J, Efferth T (2006) Microarray expression profiling of ABC transporters in human breast cancer. Cancer Genomics Proteomics 3:97–106
Girodon E, Cazeneuve C, Lebargy F, Chinet T, Costes B, Ghanem N, Martin J, Lemay S, Scheid P, Housset B, Bignon J, Goossens M (1997) CFTR gene mutations in adults with disseminated bronchiectasis. Eur J Hum Genet 5:149–155
Goda K, Bacsó Z, Szabó G (2009) Multidrug resistance through the spectacle of P-glycoprotein. Curr Cancer Drug Targets 9:281–297
Goffeau A, Park J, Paulsen IT, Jonniaux JL, Dinh T, Mordant P, Saier MH Jr (1997) Multidrug-resistant transport proteins in yeast: complete inventory and phylogenetic characterization of yeast open reading frames with the major facilitator superfamily. Yeast 13:43–54
Goldstein LJ, Galski H, Fojo A, Willingham M, Lai SL, Gazdar A, Pirker R, Green A, Crist W, Brodeur GM (1989) Expression of a multidrug resistance gene in human cancers. J Natl Cancer Inst 81:116–124
Gotoh A, Sakaeda T, Kimura T, Shirakawa T, Wada Y, Wada A, Kimachi T, Takemoto Y, Iida A, Iwakawa S, Hirai M, Tomita H, Okamura N, Nakamura T, Okumura K (2004) Antiproliferative activity of Rhinacanthus nasutus (L.) Kurz extracts and the active moiety, Rhinacanthin C. Biol Pharm Bull 27:1070–1074
Gottesman MM (1993) How cancer cells evade chemotherapy: sixteenth Richard and Hinda Rosenthal Foundation Award Lecture. Cancer Res 53:747–754
Gottesman MM, Pastan I (1993) Biochemistry of multidrug resistance mediated by the multidrug transporter. Annu Rev Biochem 62:385–427
Grant CE, Valdimarsson G, Hipfner DR, Almquist KC, Cole SPC, Deeley DR (1994) Overexpression of multidrug resistance-associated protein (MRP) increases resistance to natural product drugs. Cancer Res 54:357–361
Gu Y, Wang G, Pan G, Fawcett JP, A J, Sun J (2004) Transport and bioavailability studies of astragaloside IV, an active ingredient in Radix Astragali. Basic Clin Pharmacol Toxicol 95:295–298
Guo Y, Kotova E, Chen ZS, Lee K, Hopper-Borge E, Belinsky MG, Kruh GD (2003) MRP8, ATP-binding cassette C11 (ABCC11), is a cyclic nucleotide efflux pump and a resistance factor for fluoropyrimidines 2’,3’-dideoxycytidine and 9’-(2’-phosphonylmethoxyethyl)adenine. J Biol Chem 278:29509–29514
Hall MD, Handley MD, Gottesman MM (2009) Is resistance useless? Multidrug resistance and collateral sensitivity. Trends Pharmacol Sci 30:546–556
He L, Liu GQ (2002) Effects of various principles from Chinese herbal medicine on rhodamine123 accumulation in brain capillary endothelial cells. Acta Pharmacol Sin 23:591–596
He L, Zhao C, Yan M, Zhang LY, Xia YZ (2009) Inhibition of P-glycoprotein function by procyanidine on blood–brain barrier. Phytother Res 23:933–937
He L, Yang J, Hu L (2010) Transmembrane transport activity of paclitaxel regulated by fangchinoline in MDR1-mDCK II cells [Article in Chinese]. Zhongguo Zhong Yao Za Zhi 35:1478–1481
Heijn M, Hooijberg JH, Scheffer GL, Szabo G, Westerhoff HV, Lankelma J (1997) Anthracyclines modulate multidrug resistance protein (MRP) mediated organic anion transport. Biochim Biophys Acta 1326:12–22
Herweijer H, Sonneveld P, Baas F, Nooter KH, Herweijer P, Sonneveld F, Baas KN (1990) Expression of mdr1 and mdr3 multidrug-resistance genes in human acute and chronic leukemias and association with stimulation of drug accumulation by cyclosporine. J Natl Cancer Inst 82:1133–1140
Higgins CF (1995) The ABC of channel regulation. Cell 82:693–696
Higgins CF, Gottesman MM (1992) Is the multidrug transporter a flippase? Trends Biochem Sci 17:18–21
Higgins CF, Linton KJ (2004) The ATP switch model for ABC transporters. Nat Struct Mol Biol 11:918–926
Hill BT, Deuchars K, Hosking LK, Ling V, Whelan RDH (1990) Overexpression of P-glycoprotein in mammalian tumor cell lines after fractionated X irradiation in vitro. J Natl Cancer Inst 82:607–612
Hirohashi T, Suzuki H, Sugiyama Y (1999) ATP-dependent transport of bile salts by rat multidrug resistance-associated protein 3 (Mrp3). J Biol Chem 274:15181–15185
Hirschmann-Jax C, Foster AE, Wulf GG, Nuchtern JG, Jax TW, Gobel U, Goodell MA, Brenner MK, Hirschmann-Jax C, Foster AE, Wulf GG, Nuchtern JG, Jax TW, Gobel U, Goodell MA, Brenner MK (2004) A distinct “side population” of cells with high drug efflux capacity in human tumor cells. Proc Natl Acad Sci USA 101:14228–14233
Holland JK, Glidewell O, Cooper RG (1980) Adverse effect of radiotherapy on adjuvant chemotherapy for carcinoma of the breast. Surg Gynecol Obstet 150:817–821
Holland ML, Lau DT, Allen JD, Arnold JC (2007) The multidrug transporter ABCG2 (BCRP) is inhibited by plant-derived cannabinoids. Br J Pharmacol 152:815–824
Holland ML, Allen JD, Arnold JC (2008) Interaction of plant cannabinoids with the multidrug transporter ABCC1 (MRP1). Eur J Pharmacol 591:128–131
Hopper-Borge E, Chen ZS, Shchaveleva I, Belinsky MG, Kruh GD (2004) Analysis of the drug resistance profile of multidrug resistance protein 7 (ABCC10): resistance to docetaxel. Cancer Res 64:4927–4930
Hu YJ, Shen XL, Lu HL, Zhang YH, Huang XA, Fu LC, Fong WF (2008) Tenacigenin B derivatives reverse P-glycoprotein-mediated multidrug resistance inHepG2/Dox cells. J Nat Prod 71:1049–1051
Huang Y, Anderle P, Bussey KJ, Barbacioru C, Shankavaram U, Dai Z, Reinhold WC, Papp A, Weinstein JN, Sadée W (2004) Membrane transporters and channels: role of the transportome in cancer chemosensitivity and chemoresistance. Cancer Res 64:4294–4301
Huang M, Jin J, Sun H, Liu GT (2008a) Reversal of P-glycoprotein-mediated multidrug resistance of cancer cells by five schizandrins isolated from the Chinese herb Fructus Schizandrae. Cancer Chemother Pharmacol 62:1015–1026
Huang BB, Li GF, Ren F, Tang ZK, Ma HF, Sun YB, Chen LJ, Yang L (2008b) Effect of Glycyrrhiza inflata and Daphne genkwa on permeabilities of rhodamine 123, a P-glycoprotein substrate across rat jejunum membranes in vitro [Article in Chinese]. Zhongguo Zhong Yao Za Zhi 33:2521–2526
Huang Y, Dong G, Hong X, Chai H, Yuan X (2010) Studies on reversing MDR of K562/A02 by ramification of curcumin hydrolyzed [Article in Chinese]. Zhongguo Zhong Yao Za Zhi 35:2460–2463
Ishikawa T (1992) The ATP-dependent glutathione S-conjugate export pump. Trends Biochem Sci 17:463–468
Ishikawa T, Müller M, Klunemann C, Schaub T, Keppler D (1990) ATP-dependent primary active transport of cysteinyl leukotrienes across liver canalicular membrane Role of the ATP-dependent transport system for glutathione S-conjugates. J Biol Chem 265:19279–19286
Jedlitschky G, Leier I, Buchholz U, Barnouin K, Kurz G, Keppler D (1996) Transport of glutathione, glucuronate, and sulfate conjugates by the MRP gene-encoded conjugate export pump. Cancer Res 56:988–994
Jedlitschky G, Leier I, Buchholz U, Hummel-Eisenbeiss J, Burchell B, Keppler D (1997) ATP-dependent transport of bilirubin glucuronides by the multidrug resistance protein MRP1 and its hepatocyte canalicular isoform MRP2. Biochem J 327:305–310
Jing J, Zheng H, Wang J, Lin P, Zhang J, Xiong ZJ, Wu YY, Ren JJ, Yang HL, Wang XJ (2007) Growth inhibition and multidrug resistance-reversing effect of tanshinone I A on human breast cancer cell with estrogen receptor negative [Article in Chinese]. Sichuan Da Xue Xue Bao Yi Xue Ban 38:391–395
Johnsson A, Vallon-Christensson J, Strand C, Litman T, Eriksen J (2005) Gene expression profiling in chemoresistant variants of three cell lines of different origin. Anticancer Res 25:2661–2668
Juliano RL, Ling V (1976) A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim Biophys Acta 455:152–162
Kawabata S, Oka M, Shiozawa K, Tsukamoto K, Nakatomi K, Soda H, Fukuda M, Ikegami Y, Sugahara K, Yamada Y, Kamihira S, Doyle LA, Ross DD, Kohno S (2001) Breast cancer resistance protein directly confers SN-38 resistance of lung cancer cells. Biochem Biophys Res Commun 280:1216–1223
Keith WN, Brown R (1991) Carcinogenesis and the response of tumours to anticancer drugs. Anticancer Res 11:1739–1743
Kelter G, Steinbach D, Konkimalla VB, Tahara Tahara T, Taketani S, Fiebig HH, Efferth T (2007) Role of transferrin receptor and the ABC transporters ABCB6 and ABCB7 for resistance and differentiation of tumor cells towards artesunate. PLoS One 2:e798
Kitagawa S, Nabekura T, Kamiyama S (2004) Inhibition of P-glycoprotein function by tea catechins in KB-C2 cells. J Pharm Pharmacol 56:1001–1005
Kobayashi K, Sogame Y, Hayashi K, Nicotera P, Orenius S (1988) ATP stimulates the uptake of S-dinitrophenylglutathione by rat liver plasma membrane vesicles. FEBS Lett 240:55–58
Koike K, Kawabe T, Tanaka T, Toh S, Uchiumi T, Wada M, Akiyama S, Ono M, Kuwano M (1997) A canalicular multispecific organic anion transporter (cMOAT) antisense cDNA enhances drug sensitivity in human hepatic cancer cells. Cancer Res 57:5475–5479
Kool M, de Haas M, Scheffer GL, Scheper RJ, van Eijk MJ, Juijn JA, Baas F, Borst P (1997) Analysis of expression of cMOAT (MRP2), MRP3, MRP4, and MRP5, homologues of the multidrug resistance-associated protein gene (MRP1), in human cancer cell lines. Cancer Res 57:3537–3547
Kool M, van der Linden M, de Haas M, Scheffer GL, de Vree JM, Smith AJ, Jansen G, Peters GJ, Ponne N, Scheper RJ, Elferink RP, Baas F, Borst PM (1999) MRP3, an organic anion transporter able to transport anti-cancer drugs. Proc Natl Acad Sci USA 96:6914–6919
Kruh GD, Zeng H, Rea PA, Liu G, Chen ZS, Lee K, Belinsky MG (2001) MRP subfamily transporters and resistance to anticancer agents. J Bioenerg Biomembr 33:493–501
Kruijtzer CM, Beijnen JH, Rosing H, ten Bokkel Huinink WW, Schot M, Jewell RC, Paul EM, Schellens JH (2002) Increased oral bioavailability of topotecan in combination with the breast cancer resistance protein and P-glycoprotein inhibitor GF120918. J Clin Oncol 20:2943–2950
Kuss BJ, O’Neill GM, Eyre H, Doggett NA, Callen DF, Davey RA (1998) ARA, a novel ABC transporter, is located at 16p13.1, is deleted in inv(16) leukemias, and is shown to be expressed in primitive hematopoietic precursors. Genomics 51:455–458
Laing NM, Belinsky MG, Kruh GD, Bell DW, Boyd JT, Barone L, Testa JR, Tew KD (1998) Amplification of the ATP-binding cassette 2 transporter gene is functionally linked with enhanced efflux of estramustine in ovarian carcinoma cells. Cancer Res 58:1332–1337
Lan K, He JL, Tian Y, Tan F, Jiang XH, Wang L, Ye LM (2008) Intra-herb pharmacokinetics interaction between quercetin and isorhamentin. Acta Pharmacol Sin 29:1376–1382
Łania-Pietrzak B, Hendrich AB, Zugaj J, Michalak K (2005a) Metabolic O-demethylation does not alter the influence of isoflavones on the biophysical properties of membranes and MRP1-like protein transport activity. Arch Biochem Biophys 433:428–434
Łania-Pietrzak B, Michalak K, Hendrich AB, Mosiadz D, Grynkiewicz G, Motohashi N, Shirataki Y (2005b) Modulation of MRP1 protein transport by plant, and synthetically modified flavonoids. Life Sci 77:1879–1891
LeBlanc MJ, Brunet S, Bouchard G, Lamireau T, Yousef IM, Gavino V, Lévy E, Tuchweber B (2003) Effects of dietary soybean lecithin on plasma lipid transport and hepatic cholesterol metabolism in rats. J Nutr Biochem 14:40–48
Lee Y, Yeo H, Liu SH, Jiang Z, Savizky RM, Austin DJ, Cheng YC (2004) Increased anti-P-glycoprotein activity of baicalein by alkylation on the A ring. J Med Chem 47:5555–5566
Lee SH, Kim HJ, Lee JS, Lee IS, Kang BY (2007) Inhibition of topoisomerase I activity and efflux drug transporters' expression by xanthohumol. from hops. Arch Pharm Res 30:1435–1439
Leier I, Jedlitschky G, Buchholz U, Center M, Cole SPC, Deeley RG, Keppler D (1996) ATP-dependent glutathione disulphide transport mediated by the MRP gene-encoded conjugate export pump. Biochem J 314:433–437
Leung PH, Zhang L, Zuo Z, Lin G (2006) Intestinal absorption of Stemona alkaloids in a Caco-2 cell model. Planta Med 72:211–216
Li GH, Sun FJ, Chen F, Yang SB, Zhang J (2007a) Effect on mouse S180 MDR tumour cell expression correlated factorial matter by 70 % ethanol with Huanglian Jiedu Tang [Article in Chinese]. Zhongguo Zhong Yao Za Zhi 32:1906–1908
Li L, Pan Q, Sun M, Lu Q, Hu X (2007b) Dibenzocyclooctadiene lignans: a class of novel inhibitors of multidrug resistance-associated protein 1. Life Sci 80:741–748
Li L, Stanton JD, Tolson AH, Luo Y, Wang H (2009a) Bioactive terpenoids and flavonoids from Ginkgo biloba extract induce the expression of hepatic drug-metabolizing enzymes through pregnane X receptor, constitutive androstane receptor, and aryl hydrocarbon receptor-mediated pathways. Pharm Res 26:872–882
Li SL, Huang ZN, Hsieh HH, Yu WC, Tzeng WY, Lee GY, Chen YP, Chang CY, Chuu JJ (2009b) The augmented anti-tumor effects of Antrodia camphorata co-fermented with Chinese medicinal herb in human hepatoma cells. Am J Chin Med 37:771–783
Li Y, Wang Q, Yao X, Li Y (2010) Induction of CYP3A4 and MDR1 gene expression by baicalin, baicalein, chlorogenic acid, and ginsenoside Rf through constitutive androstane receptor- and pregnane X receptor-mediated pathways. Eur J Pharmacol 640:46–54
Liang G, Tang A, Lin X, Li L, Zhang S, Huang Z, Tang H, Li QQ (2010) Green tea catechins augment the antitumor activity of doxorubicin in an in vivo mouse model for chemoresistant liver cancer. Int J Oncol 37:111–123
Lin HL, Liu TY, Lui WY, Chi CW (1999a) Up-regulation of multidrug resistance transporter expression by berberine in human and murine hepatoma cells. Cancer 85:1937–1942
Lin HL, Liu TY, Wu CW, Chi CW (1999b) Berberine modulates expression of mdr1 gene product and the responses of digestive track cancer cells to Paclitaxel. Br J Cancer 81:416–422
Loe DW, Almquist KC, Ceeley RG, Cole SPC (1996) Multidrug resistance protein (MRP)-mediated transport of leukotriene C4 and chemotherapeutic agents in membrane vesicles. Demonstration of glutathione-dependent vincristine transport. J Biol Chem 271:9675–9682
Loe DW, Stewart RK, Massey TE, Deeley RG, Cole SPC (1997) ATP-dependent transport of aflatoxin B1 and its glutathione conjugates by the product of the multidrug resistance protein (MRP) gene. Mol Pharmacol 51:1034–1041
Loe DW, Deeley RG, Cole SPC (1998) Characterization of vincristine transport by the M(r) 190,000 multidrug resistance protein (MRP): evidence for cotransport with reduced glutathione. Cancer Res 58:5130–5136
Longhurst TJ, O’Neill GM, Harvie RM, Davey RA (1996) The anthracycline resistance-associated (ara) gene, a novel gene associated with multidrug resistance in a human leukaemia cell line. Br J Cancer 74:1331–1335
Loo TW, Bartlett MC, Clarke DM (2004) Disulfide cross-linking analysis shows that transmembrane segments 5 and 8 of human P-glycoprotein are close together on the cytoplasmic side of the membrane. J Biol Chem 279:7692–7697
Ma J, Maliepaard M, Nooter K, Loos WJ, Kolker HJ, Verweij J, Stoter G, Schellens JH (1998) Reduced cellular accumulation of topotecan: a novel mechanism of resistance in a human ovarian cancer cell line. Br J Cancer 77:1645–1652
Madgula VL, Avula B, Choi YW, Pullela SV, Khan IA, Walker LA, Khan SI (2008) Transport of Schisandra chinensis extract and its biologically-active constituents across Caco-2 cell monolayers - an in-vitro model of intestinal transport. J Pharm Pharmacol 60:363–370
Mahringer A, Karamustafa S, Klotz D, Kahl S, Konkimala VB, Wang YF, Wang JS, Liu H-Y, Boechzelt H, Hao XJ, Bauer R, Fricker G, Efferth T (2010) Inhibition of P-glycoprotein at the Blood–Brain Barrier by Phytochemicals Derived from Traditional Chinese Medicine. Cancer Genomics Proteomics 7:191–206
Majumder S, Dutta P, Mukherjee P, Datta ER, Efferth T, Bhattacharya S, Choudhuri SK (2006) Reversal of drug resistance in P-glycoprotein-expressing T-cell acute lymphoblastic CEM leukemia cells by copper N-(2-hydroxy acetophenone) glycinate and oxalyl bis (N-phenyl) hydroxamic acid. Cancer Lett 244:16–23
Maliepaard M, van Gastelen MA, de Jong LA, Pluim D, van Waardenburg RC, Ruevekamp-Helmers MC, Floot BG, Schellens JH (1999) Overexpression of the BCRP/MXR/ABCP gene in a topotecan-selected ovarian tumor cell line. Cancer Res 59:4559–4563
Mayer R, Kartenbeck J, Büchler M, Jedlitschky G, Leier I, Keppler D (1995) Expression of the MRP gene-encoded conjugate export pump in liver and its selective absence from the canalicular membrane in transport-deficient mutant hepatocytes. J Cell Biol 131:137–150
Mei Y, Qian F, Wei D, Liu J (2004) Reversal of cancer multidrug resistance by green tea polyphenols. J Pharm Pharmacol 56:1307–1314
Michaelis S, Berkower C (1995) Sequence comparison of yeast ATP-binding cassette proteins. Cold Spring Harb Symp Quant Biol 60:291–307
Mickley LA, Spengler BA, Knutsen TA, Biedler JL, Fojo AT (1997) Gene rearrangement: a novel mechanism for MDR-1 gene activation. J Clin Invest 99:1947–1957
Min YD, Yang MC, Lee KH, Kim KR, Choi SU, Lee KR (2006) Protoberberine alkaloids and their reversal activity of P-gp expressed multidrug resistance (MDR) from the rhizome of Coptis japonica Makino. Arch Pharm Res 29:757–761
Minemura M, Tanimura H, Tabor E (1999) Overexpression of multidrug resistance genes MDR1 and cMOAT in human hepatocellular carcinoma and hepatoblastoma cell lines. Int J Oncol 15:559–563
Miyake K, Mickley L, Litman T, Zhan Z, Robey R, Cristensen B, Brangi M, Greenberger L, Dean M, Fojo T, Bates SE (1999) Molecular cloning of cDNAs which are highly overexpressed in mitoxantrone-resistant cells: demonstration of homology to ABC transport genes. Cancer Res 59:8–13
Molnár J, Engi H, Hohmann J, Molnár P, Deli J, Wesolowska O, Michalak K, Wang Q (2010) Reversal of multidrug resitance by natural substances from plants. Curr Top Med Chem 10:1757–1768
Mukai R, Satsu H, Shimizu M, Ashida H (2009) Inhibition of P-glycoprotein enhances the suppressive effect of kaempferol on transformation of the aryl hydrocarbon receptor. Biosci Biotechnol Biochem 73:1635–1639
Murakami T, Takano M (2008) Intestinal efflux transporters and drug absorption. Expert Opin Drug Metab Toxicol 4:923–939
Nabekura T, Yamaki T, Ueno K, Kitagawa S (2008) Inhibition of P-glycoprotein and multidrug resistance protein 1 by dietary phytochemicals. Cancer Chemother Pharmacol 62:867–873
Nakayama M, Wada M, Harada T, Nagayama J, Kusaba H, Ohshima K, Kozuru M, Komatsu H, Ueda R, Kuwano M (1998) Hypomethylation status of CpG sites at the promoter region and overexpression of the human MDR1 gene in acute myeloid leukemias. Blood 92:4296–4307
Naramoto H, Uematsu T, Uchihashi T, Doto R, Matsuura T, Usui Y, Uematsu S, Li X, Takahashi M, Yamaoka M, Furusawa K (2007) Multidrug resistance-associated protein 7 expression is involved in cross-resistance to docetaxel in salivary gland adenocarcinoma cell lines. Int J Oncol 30:393–401
Netsch MI, Gutmann H, Luescher S, Brill S, Schmidlin CB, Kreuter MH, Drewe J (2005) Inhibitory activity of a green tea extract and some of its constituents on multidrug resistance-associated protein 2 functionality. Planta Med 71:135–141
Nguyen VT, Darbour N, Bayet C, Doreau A, Raad I, Phung BH, Dumontet C, Di Pietro A, Dijoux-Franca MG, Guilet D (2009) Selective modulation of P-glycoprotein activity by steroidal saponines from Paris polyphylla. Fitoterapia 80:39–42
Nicolle E, Boccard J, Guilet D, Dijoux-Franca MG, Zelefac F, Macalou S, Grosselin J, Schmidt J, Carrupt PA, Di Pietro A, Boumendjel A (2009) Breast cancer resistance protein (BCRP/ABCG2): new inhibitors and QSAR studies by a 3D linear solvation energy approach. Eur J Pharm Sci 38:39–46
Nikaido H (1994) Prevention of drug access to bacterial targets: permeability barriers and active efflux. Science 264:382–388, Review
Nishimura N (2005) Effects of Chinese herbal medicines on intestinal drug absorption [Article in Japanese]. Yakugaku Zasshi 125:363–369
Nobili S, Landini I, Giglioni B, Mini E (2006) Pharmacological strategies for overcoming multidrug resistance. Curr Drug Targets 7:861–879
Norwood K, Wang RY, Hirschmann-Jax C, Andreeff M, Brenner MK, Goodell MA, Wulf GG (2004) An in vivo propagated human acute myeloid leukemia expressing ABCA3. Leuk Res 28:295–299
O’Leary KA, Day AJ, Needs PW, Mellon FA, O’Brien NM, Williamson G (2003) Metabolism of quercetin-7- and quercetin-3-glucuronides by an in vitro hepatic model: the role of human beta-glucuronidase, sulfotransferase, catechol-O-methyltransferase and multi-resistant protein 2 (MRP2) in flavonoid metabolism. Biochem Pharmacol 65:479–491
Oguri T, Bessho Y, Achiwa H, Ozasa H, Maeno K, Maeda H, Sato S, Ueda R, Oguri T, Bessho Y, Achiwa H, Ozasa H, Maeno K, Maeda H, Sato S, Ueda R (2007) MRP8/ABCC11 directly confers resistance to 5-fluorouracil. Mol Cancer Ther 6:122–127
Osmak M, Perovic S (1989) Multiple fractions of gamma rays induced resistance to cis-dichloro-diammineplatinum (II) and methotrexate in human HeLa cells. Int J Radiat Oncol Biol Phys 16:1537–1541
Park S, Shimizu C, Shimoyama T, Takeda M, Ando M, Kohno T, Katsumata N, Kang YK, Nishio K, Fujiwara Y (2006) Gene expression profiling of ATP-binding cassette (ABC) transporters as a predictor of the pathologic response to neoadjuvant chemotherapy in breast cancer patients. Breast Cancer Res Treat 99:9–17
Patanasethanont D, Nagai J, Matsuura C, Fukui K, Sutthanut K, Sripanidkulchai BO, Yumoto R, Takano M (2007) Modulation of function of multidrug resistance associated-proteins by Kaempferia parviflora extracts and their components. Eur J Pharmacol 566:67–74
Pratt S, Shepard RL, Kandasamy RA, Johnston PA, Perry W 3rd, Dantzig AH (2005) The multidrug resistance protein 5 (ABCC5) confers resistance to 5-fluorouracil and transports its monophosphorylated metabolites. Mol Cancer Ther 4:855–863
Priebe W, Krawczyk M, Kuo MT, Yamane Y, Savaraj N, Ishikawa T (1998) Doxorubicin- and daunorubicin-glutathione conjugates, but not unconjugated drugs, competitively inhibit leukotriene C4 transport mediated by MRP/GS-X pump. Biochem Biophys Res Commun 247:859–863
Qin XL, Bi HC, Wang XD, Li JL, Wang Y, Xue XP, Chen X, Wang CX, le Xu J, Wang YT, Huang M (2010) Mechanistic understanding of the different effects of Wuzhi Tablet (Schisandra sphenanthera extract) on the absorption and first-pass intestinal and hepatic metabolism of Tacrolimus (FK506). Int J Pharm 389:114–121
Qiu W, Jiang XH, Liu CX, Ju Y, Jin JX (2009) Effect of berberine on the pharmacokinetics of substrates of CYP3A and P-gp. Phytother Res 23:1553–1558
Ramu A, Pollard HB, Rosario LM (1989) Doxorubicin resistance in P388 leukemia–evidence for reduced drug influx. Int J Cancer 44:539–547
Roninson IB, Chin JE, Choi K, Gros P, Housman DE, Fojo A, Shen D, Gottesman MM, Pastan I (1986) Proc Natl Acad Sci USA 83:4538–4542
Ross DD, Yang W, Abruzzo LV, Dalton WS, Schneider E, Lage H, Dietel M, Greenberger L, Cole SP, Doyle LA (1999) Atypical multidrug resistance: breast cancer resistance protein messenger RNA expression in mitoxantrone-selected cell lines. J Natl Cancer Inst 91:429–433
Ruetz S, Gros P, Ruetz S, Gros P (1994) Phosphatidylcholine translocase: a physiological role for the mdr2 gene. Cell 77:1071–1081
Ruiz JC, Choi K, von Hoff DD, Roninson IB, Wahl GM (1989) Autonomously replicating episomes contain mdr1 genes in a multidrug-resistant human cell line. Mol Cell Biol 9:109–115
Sadzuka Y, Yamashita Y, Kishimoto S, Fukushima S, Takeuchi Y, Sonobe T (2002) Glutamate transporter mediated increase of antitumor activity by theanine, an amino acid in green tea [Article in Japanese]. Yakugaku Zasshi 122:995–999
Saurin W, Hofnung M, Dassa E (1999) Getting in or out: early segregation between importers and exporters in the evolution of ATP-binding cassette (ABC) transporters. J Mol Evol 48:22–41
Scala S, Akhmed N, Rao US, Paull K, Lan LB, Dickstein B, Lee JS, Elgemeie GH, Stein WD, Bates SE (1997) P-glycoprotein substrates and antagonists cluster into two distinct groups. Mol Pharmacol 51:1024–1033
Schaub TP, Kartenbeck J, König J, Vogel O, Witzgall R, Kriz W, Keppler D (1997) Expression of the conjugate export pump encoded by the mrp2 gene in the apical membrane of kidney proximal tubules. J Am Soc Nephrol 8:1213–1221
Schinkel AH, Mayer U, Wagenaar E, Mol CAAM, van Deemter L (1997) Normal viability and altered pharmacokinetics in mice lacking mdr1-type (drug-transporting) P-glycoproteins. Proc Natl Acad Sci USA 94:4028–4032
Shen X, Chen G, Zhu G, Fong WF (2006) (+/−)-3'-O, 4'-O-dicynnamoyl-cis-khellactone, a derivative of (+/−)-praeruptorin A, reverses P-glycoprotein mediated multidrug resistance in cancer cells. Bioorg Med Chem 14:7138–7145
Shen H, Xu W, Chen Q, Wu Z, Tang H, Wang F (2010) Tetrandrine prevents acquired drug resistance of K562 cells through inhibition of mdr1 gene transcription. J Cancer Res Clin Oncol 136:659–665
Sikic BI (1993) Modulation of multidrug resistance: at the threshold. J Clin Oncol 11:1629–1635
Sklar MD (1988) Increased resistance to cis-diamminedichloroplatinum(II) in NIH 3 T3 cells transformed by ras oncogenes. Cancer Res 48:793–797
Slovak ML, Hoeltge GA, Trent JM (1987) Cytogenetic alterations associated with the acquisition of doxorubicin resistance: possible significance of chromosome 7 alterations. Cancer Res 47:6646–6652
Smit JJ, Schinkel AH, Oude Elferink RP, Groen AK, Wagenaar E, van Deemter L, Mol CA, Ottenhoff R, van der Lugt NM, van Roon MA (1993) Homozygous disruption of the murine mdr2 P-glycoprotein gene leads to a complete absence of phospholipid from bile and to liver disease. Cell 75:451–462
Smith AJ, van Helvoort A, van Meer G, Szabo K, Welker E, Szakacs G, Varadi A, Sarkadi B, Borst P (2000) MDR3 P-glycoprotein, a phosphatidylcholine translocase, transports several cytotoxic drugs and directly interacts with drugs as judged by interference with nucleotide trapping. J Biol Chem 275:23530–23539
Steinbach D, Gillet JP, Sauerbrey A, Gruhn B, Dawczynski K, Bertholet V, de Longueville F, Zintl F, Remacle J, Efferth T (2006) ABCA3 as a possible cause of drug resistance in childhood acute myeloid leukemia. Clin Cancer Res 12:4357–4363
Sun M, Xu X, Lu Q, Pan Q, Hu X (2007) Schisandrin B: a dual inhibitor of P-glycoprotein and multidrug resistance-associated protein 1. Cancer Lett 246:300–307
Suzuki H, Tanabe H, Mizukami H, Inoue M (2010) Selective regulation of multidrug resistance protein in vascular smooth muscle cells by the isoquinoline alkaloid coptisine. Biol Pharm Bull 33:677–682
Takahashi T, Kaku T, Sato T, Watanabe K, Sato J (2010) Effects of Acanthopanax senticosus HARMS extract on drug transport in human intestinal cell line Caco-2. J Nat Med 64:55–62
Takara K, Sakaeda T, Okumura K (2006) An update on overcoming MDR1-mediated multidrug resistance in cancer chemotherapy. Curr Pharm Des 12:273–286
Tamaki H, Satoh H, Hori S, Ohtani H, Sawada Y (2010) Inhibitory effects of herbal extracts on breast cancer resistance protein (BCRP) and structure-inhibitory potency relationship of isoflavonoids. Drug Metab Pharmacokinet 25:170–179
Tammur J, Prades C, Arnould I, Rzhetsky A, Hutchinson A, Adachi M, Schuetz JD, Swoboda KJ, Ptácek LJ, Rosier M, Dean M, Allikmets R (2001) Two new genes from the human ATP-binding cassette transporter superfamily, ABCC11 and ABCC12, tandemly duplicated on chromosome 16q12. Gene 273:89–96
Taniguchi K, Wada M, Kohno K, Nakamura T, Kawabe T, Kawakami M, Kagotani K, Okumura K, Akiyama S, Kuwano M (1996) A human canalicular multispecific organic anion transporter (cMOAT) gene is overexpressed in cisplatin-resistant human cancer cell lines with decreased drug accumulation. Cancer Res 56:4124–4129
Tian Q, Zhang J, Tan TM, Chan E, Duan W, Chan SY, Boelsterli UA, Ho PC, Yang H, Bian S, Huang M, Zhu YZ, Xiong W, Li X, Zhou S (2005) Human multidrug resistance associated protein 4 confers resistance to camptothecins. Pharm Res 22:1837–1853
Tian Q, Zhang J, Chan SY, Tan TM, Duan W, Huang M, Zhu YZ, Chan E, Yu Q, Nie YQ, Ho PC, Li Q, Ng KY, Yang HY, Wei H, Bian JS, Zhou SF (2006) Topotecan is a substrate for multidrug resistance associated protein 4. Curr Drug Metab 7:105–118
Tiwari AK, Sodani K, Dai CL, Ashby CR Jr, Chen ZS (2011) Revisiting the ABCs of multidrug resistance in cancer chemotherapy. Curr Pharm Biotechnol 12(4):570–594
Tsai PL, Tsai TH (2004a) Hepatobiliary excretion of berberine. Drug Metab Dispos 32:405–412
Tsai PL, Tsai TH (2004b) Pharmacokinetics of baicalin in rats and its interactions with cyclosporin A, quinidine and SKF-525A: a microdialysis study. Planta Med 70:1069–1074
Tsai TH, Wu JW (2003) Regulation of hepatobiliary excretion of sinomenine by P-glycoprotein in Sprague–Dawley rats. Life Sci 72:2413–2426
Ueda K, Cardarelli C, Gottesman MM, Pastan I (1987) Expression of a full-length cDNA for the human “MDR1” gene confers resistance to colchicine, doxorubicin, and vinblastine. Proc Natl Acad Sci USA 84:3004–3008
Vaidyanathan JB, Walle T (2001) Transport and metabolism of the tea flavonoid (−)-epicatechin by the human intestinal cell line Caco-2. Pharm Res 18:1420–1425
Vaidyanathan JB, Walle T (2003) Cellular uptake and efflux of the tea flavonoid (−)epicatechin-3-gallate in the human intestinal cell line Caco-2. J Pharmacol Exp Ther 307:745–752
van der Bliek AM, Baas F, Houte T, de Lange T, Koolman PM, van der Velde-Koerts T, Borst P (1987) The human mdr3 gene encodes a novel P-glycoprotein homologue and gives rise to alternatively spliced mRNAs in liver. EMBO J 6:3325–3331
Volm M, Zerban H, Mattern J, Efferth T (1990) Overexpression of P-glycoprotein in rat hepatocellular carcinomas induced with N-nitrosomorpholine. Carcinogenesis 11:169–172
Volm M, Wagner-Pommerenke EW, Efferth T, Löhrke H, Mattern J (1991) Circumvention of multi-drug resistance in human kidney and kidney carcinoma in vitro. Cancer 67:2484–2489
Vulevic B, Chen Z, Boyd JT, Davis W Jr, Walsh ES, Belinsky MG, Tew KD (2001) Cloning and characterization of human adenosine 5Vtriphosphate-binding cassette, sub-family A, transporter 2 (ABCA2). Cancer Res 61:3339–3347
Walle UK, Galijatovic A, Walle T (1999) Transport of the flavonoid chrysin and its conjugated metabolites by the human intestinal cell line Caco-2. Biochem Pharmacol 58:431–438
Wan CK, Zhu GY, Shen XL, Chattopadhyay A, Dey S, Fong WF (2006) Gomisin A alters substrate interaction and reverses P-glycoprotein-mediated multidrug resistance in HepG2-DR cells. Biochem Pharmacol 72:824–837
Wang X, Morris ME (2007) Effects of the flavonoid chrysin on nitrofurantoin pharmacokinetics in rats: potential involvement of ABCG2. Drug Metab Dispos 35:268–274
Wang TX, Yang XH (2008) Reversal effect of isotetrandrine, an isoquinoline alkaloid extracted from Caulis Mahoniae, on P-glycoprotein-mediated doxorubicin-resistance in human breast cancer (MCF-7/DOX) cells. Yao Xue Xue Bao 43:461–466
Wang EJ, Barecki-Roach M, Johnson WW (2002) Elevation of P-glycoprotein function by a catechin in green tea. Biochem Biophys Res Commun 297:412–418
Wang C, Zhang JX, Shen XL, Wan CK, Tse AK, Fong WF (2004) Reversal of P-glycoprotein-mediated multidrug resistance by Alisol B 23-acetate. Biochem Pharmacol 68:843–855
Wang J, Xia Y, Wang H, Hou Z (2007) Chinese herbs of Shenghe Powder reverse multidrug resistance of gastric carcinoma SGC-7901. Integr Cancer Ther 6:400–404
Wang SW, Chen Y, Joseph T, Hu M (2008) Variable isoflavone content of red clover products affects intestinal disposition of biochanin A, formononetin, genistein, and daidzein. J Altern Complement Med 14:287–297
Wang W, Sun YP, Huang XZ, He M, Chen YY, Shi GY, Li H, Yi J, Wang J (2010a) Emodin enhances sensitivity of gallbladder cancer cells to platinum drugs via glutathion depletion and MRP1 downregulation. Biochem Pharmacol 79:1134–1140
Wang XB, Wang SS, Zhang QF, Liu M, Li HL, Liu Y, Wang JN, Zheng F, Guo LY, Xiang JZ (2010b) Inhibition of tetramethylpyrazine on P-gp, MRP2, MRP3 and MRP5 in multidrug resistant human hepatocellular carcinoma cells. Oncol Rep 23:211–215
Wijnholds J, Scheffer GL, van der Valk M, Beijnen JH, Scheper RJ, Borst P (1998) Multidrug resistance protein 1 protects the oropharyngeal mucosal layer and the testicular tubules against drug-induced damage. J Exp Med 188:797–808
Wong VK, Chiu P, Chung SS, Chow LM, Zhao YZ, Yang BB, Ko BC (2005) Pseudolaric acid B, a novel microtubule-destabilizing agent that circumvents multidrug resistance phenotype and exhibits antitumor activity in vivo. Clin Cancer Res 11:6002–6011
Wu JY, Fong WF, Zhang JX, Leung CH, Kwong HL, Yang MS, Li D, Cheung HY (2003) Reversal of multidrug resistance in cancer cells by pyranocoumarins isolated from Radix Peucedani. Eur J Pharmacol 473:9–17
Wu CP, Calcagno AM, Hladky SB, Ambudkar SV, Barrand MA (2005) Modulatory effects of plant phenols on human multidrug-resistance proteins 1, 4 and 5 (ABCC1, 4 and 5). FEBS J 272:4725–4740
Wu YT, Lin CW, Lin LC, Chiu AW, Chen KK, Tsai TH (2010) Analysis of biliary excretion of icariin in rats. J Agric Food Chem 58:9905–9911
Wulf GG, Modlich S, Inagaki N, Reinhardt D, Schroers R, Griesinger F, Trümper L (2004) ABC transporter ABCA3 is expressed in acute myeloid leukemia blast cells and participates in vesicular transport. Haematologica 89:1395–1397
Xu D, Lu Q, Hu X (2006) Down-regulation of P-glycoprotein expression in MDR breast cancer cell MCF-7/ADR by honokiol. Cancer Lett 243:274–280
Yamano G, Funahashi H, Kawanami O, Zhao LX, Ban N, Uchida Y, Morohoshi T, Ogawa J, Shioda S, Inagaki N (2001) ABCA3 is a lamellar body membrane protein in human lung alveolar type II cells. FEBS Lett 508:221–225
Yang CH, Schneider E, Kuo ML, Volk EL, Rocchi EM, Chen YC (2000) BCRP/MXR/ABCP expression in topotecan-resistant human breast carcinoma cells. Biochem Pharmacol 60:831–837
Yang XW, Guo QM, Wang Y (2008) Absorption and transport of 6 coumarins isolated from the roots of Angelica pubescens f. biserrata in human Caco-2 cell monolayer model (Article in Chinese). Zhong Xi Yi Jie He Xue Bao. 6(4):392–8
Yang CY, Chao PD, Hou YC, Tsai SY, Wen KC, Hsiu SL (2008a) Marked decrease of cyclosporin bioavailability caused by coadministration of ginkgo and onion in rats. Food Chem Toxicol 44:1572–1578
Yang XW, Guo QM, Wang Y (2008b) Absorption and transport of 6 coumarins isolated from the roots of Angelica pubescens f. biserrata in human Caco-2 cell monolayer model. [Article in Chinese]. Zhong Xi Yi Jie He Xue Bao 6:392–398
Yao HW, Fu XY, Xie QD, Huang BB, Sun YB, Li GF (2009) Effect of liquorice decoction on rat intestinal P-glycoprotein [Article in Chinese]. Nan Fang Yi Ke Da Xue Xue Bao 29:1571–1573
Yasui K, Mihara S, Zhao C, Okamoto H, Saito-Ohara F, Tomida A, Funato T, Yokomizo A, Naito S, Imoto I, Tsuruo T, Inazawa J (2004) Alteration in copy numbers of genes as a mechanism for acquired drug resistance. Cancer Res 64:1403–1410
Yi HJ, Oh JH, Lee YJ (2010) Absence of drug interaction between Hwang-Ryun-Hae-Dok-Tang and phenolsulfonphthalein. Arch Pharm Res 33:2025–2031
Yokooji T, Kida M, Mori M, Akashi H, Mori N, Yoshihara S, Murakami T (2010) Interaction of Rhei Rhizoma extract with cytochrome P450 3A and efflux transporters in rats. Pharmazie 65:367–374
You HS, Zhang HF, Dong YL, Chen SY, Wang MY, Dong WH, Xing JF (2010) Absorption and transportation characteristics of scutellarin and scutellarein across Caco-2 monolayer model. [Article in Chinese]. Zhong Xi Yi Jie He Xue Bao 8:863–869
Yu XY, Lin SG, Chen X, Zhou ZW, Liang J, Duan W, Chowbay B, Wen JY, Chan E, Cao J, Li CG, Zhou SF (2007a) Transport of cryptotanshinone, a major active triterpenoid in Salvia miltiorrhiza Bunge widely used in the treatment of stroke and Alzheimer's disease, across the blood–brain barrier. Curr Drug Metab 8:365–378
Yu XY, Lin SG, Zhou ZW, Chen X, Liang J, Yu XQ, Chowbay B, Wen JY, Duan W, Chan E, Li XT, Cao J, Li CG, Xue CC, Zhou SF (2007b) Role of P-glycoprotein in limiting the brain penetration of glabridin, an active isoflavan from the root of Glycyrrhiza glabra. Pharm Res 24:1668–1690
Yu XY, Lin SG, Zhou ZW, Chen X, Liang J, Liu PQ, Duan W, Chowbay B, Wen JY, Li CG, Zhou SF (2007c) Role of P-glycoprotein in the intestinal absorption of tanshinone IIA, a major active ingredient in the root of Salvia miltiorrhiza Bunge. Curr Drug Metab 8:325–340
Yu XY, Zhou ZW, Lin SG, Chen X, Yu XQ, Liang J, Duan W, Wen JY, Li XT, Zhou SF (2007d) Role of ATP-binding cassette drug transporters in the intestinal absorption of tanshinone IIB, one of the major active diterpenoids from the root of Salvia miltiorrhiza. Xenobiotica 37:375–415
Yu S, Yu Y, Liu L, Wang X, Lu S, Liang Y, Liu X, Xie L, Wang G (2010) Increased plasma exposures of five protoberberine alkaloids from Coptidis Rhizoma in streptozotocin-induced diabetic rats: is P-GP involved? Planta Med 76:876–881
Zaman GJR, Flens MJ, van Leusden MR, de Haas M, Mülder HS, Lankelma J, Pinedo HM, Scheper RJ, Baas F, Broxterman HJ (1994) The human multidrug resistance-associated protein MRP is a plasma membrane drug-efflux pump. Proc Natl Acad Sci USA 91:8822–8826
Zelcer N, Saeki T, Reid G, Beijnen JH, Borst P, Zelcer N, Saeki T, Reid G, Beijnen JH, Borst P (2001) Characterization of drug transport by the human multidrug resistance protein 3 (ABCC3). J Biol Chem 276:46400–46407
Zeng H, Bain LJ, Belinsky MG, Kruh GD (1999) Expression of multidrug resistance protein-3 (multispecific organic anion transporter-D) in human embryonic kidney 293 cells confers resistance to anticancer agents. Cancer Res 59:5964–5967
Zeng H, Chen ZS, Belinsky MG, Rea PA, Kruh GD, Zeng H, Chen ZS, Belinsky MG, Rea PA, Kruh GD (2001) Transport of methotrexate (MTX) and folates by multidrug resistance protein (MRP) 3 and MRP1: effect of polyglutamylation on MTX transport. Cancer Res 61:7225–7232
Zhang JP, Ying K, Xiao ZY, Zhou B, Huang QS, Wu HM, Yin M, Xie Y, Mao YM, Rui YC (2004a) Analysis of gene expression profiles in human HL-60 cell exposed to cantharidin using cDNA microarray. Int J Cancer 108:212–218
Zhang S, Yang X, Morris ME (2004b) Combined effects of multiple flavonoids on breast cancer resistance protein (ABCG2)-mediated transport. Pharm Res 21:1263–1273
Zhang S, Wang X, Sagawa K, Morris ME (2005a) Flavonoids chrysin and benzoflavone, potent breast cancer resistance protein inhibitors, have no significant effect on topotecan pharmacokinetics in rats or mdr1a/1b (−/−) mice. Drug Metab Dispos 33:341–348
Zhang S, Yang X, Coburn RA, Morris ME (2005b) Structure activity relationships and quantitative structure activity relationships for the flavonoid-mediated inhibition of breast cancer resistance protein. Biochem Pharmacol 70:627–639
Zhang J, Huang M, Guan S, Bi HC, Pan Y, Duan W, Chan SY, Chen X, Hong YH, Bian JS, Yang HY, Zhou S (2006) A mechanistic study of the intestinal absorption of cryptotanshinone, the major active constituent of Salvia miltiorrhiza. J Pharmacol Exp Ther 317:1285–1294
Zhang DM, He ZW, Liu XD, Li Y, Xie L, Wang GJ, Liu L (2007) In-vivo and in-vitro studies on the effect of Huang-Lian-Jie-Du-Tang on nimodipine transport across rat blood–brain barrier. J Pharm Pharmacol 59:1733–1738
Zhang R, Jie J, Zhou Y, Cao Z, Li W (2009) Long-term effects of Panax ginseng on disposition of fexofenadine in rats in vivo. Am J Chin Med 37:657–667
Zhou DC, Zittoun R, Marie JP (1995) Homoharringtonine: an effective new natural product in cancer chemotherapy. Bull Cancer 82:987–995
Zhou ZW, Chen X, Liang J, Yu XY, Wen JY, Zhou SF (2007) Involvement of P-glycoprotein and multidrug resistance associated protein 1 in the transport of tanshinone IIB, a primary active diterpenoid quinone from the roots of Salvia miltiorrhiza, across the blood–brain barrier. Drug Metab Lett 1:205–217
Zhu A, Wang X, Guo Z (2001) Study of tea polyphenol as a reversal agent for carcinoma cell lines' multidrug resistance (study of TP as a MDR reversal agent). Nucl Med Biol 28:735–740
Zhu DF, Zhao XP, Cheng YY (2006) Transport mechanism of danshensu across Caco-2 monolayer model [Article in Chinese]. Zhongguo Zhong Yao Za Zhi 31:1517–1521
Zou SS, Xu R, He QY (2010) Mechanism of Chinese herbal compound Zilongjin for antagonizing multi-drug resistance of tumor cells [Article in Chinese]. Zhongguo Zhong Xi Yi Jie He Za Zhi 30:601–606
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Efferth, T. (2013). Inhibition of ATP-Binding Cassette Transporters by Chinese Herbs and Phytochemicals. In: Wagner, H., Ulrich-Merzenich, G. (eds) Evidence and Rational Based Research on Chinese Drugs. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0442-2_7
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