5,024
Views
50
CrossRef citations to date
0
Altmetric
Review Article

Advances in plant-based inhibitors of P-glycoprotein

, , , , &
Pages 867-881 | Received 19 Nov 2015, Accepted 21 Jan 2016, Published online: 02 Mar 2016

References

  • Gottesman MM, Fojo T, Bates SE. Multidrug resistance in cancer: role of ATP-dependent transporters. Nat Rev Cancer 2002;2:48–58
  • Romiti A, Cox MC, Sarcina I, et al. Metronomic chemotherapy for cancer treatment: a decade of clinical studies. Cancer Chemother Pharmacol 2013;72:13–33
  • Colabufo NA, Pagliarulo V, Berardi F, et al. Bicalutamide failure in prostate cancer treatment: involvement of Multi Drug Resistance proteins. Eur J Pharmacol 2008;601:38–42
  • Elkadi OA. MDR-selective microbial-based therapy: a novel approach to cancer treatment. Med Hypotheses 2013;81:207–11
  • Huang Y, Sadee W. Drug sensitivity and resistance genes in cancer chemotherapy: a chemogenomics approach. Drug Discov Today 2003;8:356–63
  • Montazami N, Aghapour M, Farajnia S, et al. New insights into the mechanisms of multidrug resistance in cancers. Cell Mol Biol (Noisy-le-grand) Mol 2015;61:70–80
  • Gatouillat G, Magid AA, Bertin E, et al. Medicarpin and millepurpan, two flavonoids isolated from Medicago sativa, induce apoptosis and overcome multidrug resistance in leukemia P388 cells. Phytomedicine 2015;22:1186–94
  • Ji M, Shi Y, Lou H, et al. Overcoming of P-glycoprotein-mediated multidrug resistance in K562/A02 cells using riccardin F and pakyonol, bisbibenzyl derivatives from liverworts. Biosci Trends 2011;5:192–7
  • Leslie EM, Deeley RG, Cole SP. Multidrug resistance proteins: role of P-glycoprotein, MRP1, MRP2, and BCRP (ABCG2) in tissue defense. Toxicol Appl Pharmacol 2005;204:216–37
  • Ling V, Thompson LH. Reduced permeability in CHO cells as a mechanism of resistance to colchicine. J Cell Physiol 1974;83:103–16
  • Schinkel AH1, Jonker JW. Mammalian drug efflux transporters of the ATP binding cassette (ABC) family: an overview. Adv Drug Deliv Rev 2003;55:3–29
  • Gottesman MM, Ling V. The molecular basis of multidrug resistance in cancer: the early years of P-glycoprotein research. FEBS Lett 2006;580:998–1009
  • Palmeira A, Sousa E, Vasconcelos MH, et al. Three decades of P-gp inhibitors: skimming through several generations and scaffolds. Curr Med Chem 2012;19:1946–2025
  • Sarisozen C, Vural I, Levchenko T, et al. PEG-PE-based micelles co-loaded with paclitaxel and cyclosporine A or loaded with paclitaxel and targeted by anticancer antibody overcome drug resistance in cancer cells. Drug Deliv 2012;19:169–76
  • Tsuruo T, Iida H, Tsukagoshi S, Sakurai Y. Overcoming of vincristine resistance in P388 leukemia in vivo and in vitro through enhanced cytotoxicity of vincristine and vinblastine by verapamil. Cancer Res 1981;41:1967–72
  • Safa AR. Photoaffinity labeling of the multidrug-resistance-related P-glycoprotein with photoactive analogs of verapamil. Proc Natl Acad Sci USA 1988;85:7187–91
  • Shiraga K, Sakaguchi K, Senoh T, et al. Modulation of doxorubicin sensitivity by cyclosporine A in hepatocellular carcinoma cells and their doxorubicin-resistant sublines. J Gastroenterol Hepatol 2001;16:460–6
  • Angelini A, Iezzi M, Di Febbo C, et al. Reversal of P-glycoprotein-mediated multidrug resistance in human sarcoma MES-SA/Dx-5 cells by nonsteroidal anti-inflammatory drugs. Oncol Rep 2008;20:731–5
  • Pearce HL, Safa AR, Bach NJ, et al. Essential features of the P-glycoprotein pharmacophore as defined by a series of reserpine analogs that modulate multidrug resistance. Proc Natl Acad Sci USA 1989;86:5128–32
  • Kalitsky-Szirtes J, Shayeganpour A, Brocks DR, et al. Suppression of drug-metabolizing enzymes and efflux transporters in the intestine of endotoxin-treated rats. Drug Metab Dispos 2004;32:20–7
  • Liu ZH, Ma YL, He YP, et al. Tamoxifen reverses the multi-drug-resistance of an established human cholangiocarcinoma cell line in combined chemotherapeutics. Mol Biol Rep 2011;38:1769–75
  • Palmeira A, Rodrigues F, Sousa E, et al. New uses for old drugs: pharmacophore-based screening for the discovery of P-glycoprotein inhibitors. Chem Biol Drug Des 2011;78:57–72
  • Bark H, Choi CH. PSC833, cyclosporine analogue, downregulates MDR1 expression by activating JNK/c-Jun/AP-1 and suppressing NF-kappaB. Cancer Chemother Pharmacol 2010;65:1131–6
  • Bates SF, Chen C, Robey R, et al. Reversal of multidrug resistance: lessons from clinical oncology. Novartis Found Symp 2002;243:83–96; discussion 96–102, 180–5
  • Biscardi M, Teodori E, Caporale R, et al. Multidrug reverting activity toward leukemia cells in a group of new verapamil analogues with low cardiovascular activity. Leuk Res 2006;30:1–8
  • Lee SY, Rhee YH, Jeong SJ, et al. Hydrocinchonine, cinchonine, and quinidine potentiate paclitaxel-induced cytotoxicity and apoptosis via multidrug resistance reversal in MES-SA/DX5 uterine sarcoma cells. Environ Toxicol 2011;26:424–31
  • Pire MM, Emmert D, Hrycyna CA, et al. Inhibition of P-glycoprotein-mediated paclitaxel resistance by reversibly linked quinine homodimers. Mol Pharmacol 2009;75:92–100
  • Mistry P, Stewart AJ, Dangerfield W, et al. In vitro and in vivo reversal of P-glycoprotein-mediated multidrug resistance by a novel potent modulator, XR9576. Cancer Res 2001;61:749–58
  • Marcelletti JF, Multani PS, Lancet JE, et al. Leukemic blast and natural killer cell P-glycoprotein function and inhibition in a clinical trial of zosuquidar infusion in acute myeloid leukemia. Leuk Res 2009;33:769–74
  • Kuntner C, Bankstahl JP, Bankstahl M, et al. Dose-response assessment of tariquidar and elacridar and regional quantification of P-glycoprotein inhibition at the rat blood-brain barrier using (R)-[(11)C]verapamil PET. Eur J Nucl Med Mol Imaging 2010;37:942–53
  • Lee BD, French KJ, Zhuang Y, et al. Development of a syngeneic in vivo tumor model and its use in evaluating a novel P-glycoprotein modulator, PGP-4008. Oncol Res 2003;14:49–60
  • Pusztai L, Wagner P, Ibrahim N, et al. Phase II study of tariquidar, a selective P-glycoprotein inhibitor, in patients with chemotherapy-resistant, advanced breast carcinoma. Cancer 2005;104:682–91
  • Girdhani S, Bhosle SM, Thulsidas SA, et al. Potential of radiosensitizing agents in cancer chemo-radiotherapy. J Cancer Res Ther 2005;1:129–31
  • Abdallah HM, Al-Abd AM, El-Dine RS, et al. P-glycoprotein inhibitors of natural origin as potential tumor chemo-sensitizers: a review. J Adv Res 2015;6:45–62
  • Anthony V, Skach WR. Molecular mechanism of P-glycoprotein assembly into cellular membranes. Curr Protein Pept Sci 2002;3:485–501
  • Sun J, He ZG, Cheng G, et al. Multidrug resistance P-glycoprotein: crucial significance in drug disposition and interaction. Med Sci Monit 2004;10:RA5–14
  • Ambudkar SV, Kimchi-Sarfaty C, Sauna ZE, et al. P-glycoprotein: from genomics to mechanism. Oncogene 2003;22:7468–85
  • Loo TW, Clarke DM. Recent progress in understanding the mechanism of P-glycoprotein-mediated drug efflux. J Membr Biol 2005;206:173–85
  • Ferté J. Analysis of the tangled relationships between P-glycoprotein-mediated multidrug resistance and the lipid phase of the cell membrane. Eur J Biochem 2000;267:277–94
  • Ginn PE. Immunohistochemical detection of P-glycoprotein in formalin-fixed and paraffin-embedded normal and neoplastic canine tissues. Vet Pathol 1996;33:533–41
  • Borst P, Schinkel AH. P-glycoprotein ABCB1: a major player in drug handling by mammals. J Clin Invest 2013;123:4131–3
  • Mealey KL, Fidel J. P-glycoprotein mediated drug interactions in animals and humans with cancer. J Vet Intern Med 2015;29:1–6
  • Tucker TG, Milne AM, Fournel-Gigleux S, et al. Absolute immunoquantification of the expression of ABC transporters P-glycoprotein, breast cancer resistance protein and multidrug resistance-associated protein 2 in human liver and duodenum. Biochem Pharmacol 2012;83:279–85
  • Tang YZ, Li DQ, Sun FJ, et al. P-glycoprotein regulating biphasic insulin secretion in rat pancreatic beta cells. Chin Med J (Engl) 2009;122:2587–92
  • Water FM, Boleij JM, Peters JG, et al. Characterization of P-glycoprotein and multidrug resistance proteins in rat kidney and intestinal cell lines. Eur J Pharm Sci 2007;30:36–44
  • Ellis K, Marlin JW, Taylor TA, et al. The effects of human immunodeficiency virus infection on the expression of the drug efflux proteins P-glycoprotein and breast cancer resistance protein in a human intestine model. J Pharm Pharmacol 2015;67:178–88
  • Johnson WW. P-glycoprotein-mediated efflux as a major factor in the variance of absorption and distribution of drugs: modulation of chemotherapy resistance. Methods Find Exp Clin Pharmacol 2002;24:501–14
  • Huang L, Li X, Roberts J, et al. Differential role of P-glycoprotein and breast cancer resistance protein in drug distribution into brain, CSF and peripheral nerve tissues in rats. Xenobiotica 2015;45:547–55
  • Lin JH, Yamazaki M. Role of P-glycoprotein in pharmacokinetics: clinical implications. Clin Pharmacokinet 2003;42:59–98
  • Sauna ZE, Smith MM, Müller M, et al. The mechanism of action of multidrug-resistance-linked P-glycoprotein. J Bioenerg Biomembr 2001;33:481–91
  • Sharom FJ. Complex Interplay between the P-Glycoprotein multidrug efflux pump and the membrane: its role in modulating protein function. Front Oncol 2014;4:41
  • Callaghan R, Ford RC, Kerr ID. The translocation mechanism of P-glycoprotein. FEBS Lett 2006;580:1056–63
  • Orelle C, Gubellini F, Durand A, et al. Conformational change induced by ATP binding in the multidrug ATP-binding cassette transporter BmrA. Biochemistry 2008;47:2404–12
  • García-Carrasco M, Mendoza-Pinto C, Macias Díaz S, et al. P-glycoprotein in autoimmune rheumatic diseases. Autoimmun Rev 2015;14:594–600
  • Sharom FJ. The P-glycoprotein multidrug transporter. Essays Biochem 2011;50:161–78
  • Amin ML. P-glycoprotein inhibition for optimal drug delivery. Drug Target Insights 2013;7:27–34
  • Varma MV, Ashokraj Y, Dey CS, et al. P-glycoprotein inhibitors and their screening: a perspective from bioavailability enhancement. Pharmacol Res 2003;48:347–59
  • Srivalli KMR, Lakshmi PK. Overview of P-glycoprotein inhibitors: a rational outlook. Braz J Pharm Sci 2012;48:353–67
  • Pascaud C, Garrigos M, Orlowski S. Multidrug resistance transporter P-glycoprotein has distinct but interacting binding sites for cytotoxic drugs and reversing agents. Biochem J 1998;333:351–8
  • Ramachandra M, Ambudkar SV, Gottesman MM, et al. Functional characterization of a glycine 185-to-valine substitution in human P-glycoprotein by using a vaccinia-based transient expression system. Mol Biol Cell 1996;7:1485–98
  • Ambudkar SV, Kim IW, Sauna ZE. The power of the pump: mechanisms of action of P-glycoprotein (ABCB1). Eur J Pharm Sci 2006;27:392–400
  • Shapiro AB, Ling V. Effect of quercetin on Hoechst 33342 transport by purified and reconstituted P-glycoprotein. Biochem Pharmacol 1997;53:587–96
  • Hugger ED, Novak BL, Burton PS, et al. A comparison of commonly used polyethoxylated pharmaceutical excipients on their ability to inhibit P-glycoprotein activity in vitro. J Pharm Sci 2002;91:1991–2002
  • Nijveldt RJ, van Nood E, van Hoorn DE, et al. Flavonoids: a review of probable mechanisms of action and potential applications. Am J Clin Nutr 2001;74:418–25
  • Narayana KR, Reddy MS, Chaluvadi MR, et al. Bioflavonoids classification, pharmacological, biochemical effects and therapeutic potential. Ind. J Pharmacol 2001;33:2–16
  • Boumendjel A, Di Pietro A, Dumontet C, et al. Recent advances in the discovery of flavonoids and analogs with high-affinity binding to P-glycoprotein responsible for cancer cell multidrug resistance. Med Res Rev 2002;22:512–29
  • Chieli E, Romiti N, Catiana Zampini I, et al. Effects of Zuccagnia punctata extracts and their flavonoids on the function and expression of ABCB1/P-glycoprotein multidrug transporter. J Ethnopharmacol 2012;144:797–801
  • Limtrakul P, Khantamat O, Pintha K. Inhibition of P-glycoprotein function and expression by kaempferol and quercetin. J Chemother 2005;17:86–95
  • Yu CP, Wu PP, Hou YC, et al. Quercetin and rutin reduced the bioavailability of cyclosporine from Neoral, an immunosuppressant, through activating P-glycoprotein and CYP 3A4. J Agric Food Chem 2011;59:4644–8
  • Castro AF, Altenberg GA. Inhibition of drug transport by genistein in multidrug-resistant cells expressing P-glycoprotein. Biochem Pharmacol 1997;53:89–93
  • Sun L, Chen W, Qu L, et al. Icaritin reverses multidrug resistance of HepG2/ADR human hepatoma cells via downregulation of MDR1 and P-glycoprotein expression. Mol Med Rep 2013;8:1883–7
  • Li C, Kim M, Choi H, Choi J. Effects of baicalein on the pharmacokinetics of tamoxifen and its main metabolite, 4-hydroxytamoxifen, in rats: possible role of cytochrome P450 3A4 and P-glycoprotein inhibition by baicalein. Arch Pharm Res 2011;34:1965–72
  • Zhang S, Morris ME. Effects of the flavonoids biochanin A, morin, phloretin, and silymarin on P-glycoprotein-mediated transport. J Pharmacol Exp Ther 2003;304:1258–67
  • Lee E, Enomoto R, Koshiba C, et al. Inhibition of P-glycoprotein by wogonin is involved with the potentiation of etoposide-induced apoptosis in cancer cells. Ann N Y Acad Sci 2009;1171:132–6
  • Shapiro AB, Ling V. Reconstitution of drug transport by purified P-glycoprotein. J Biol Chem 1995;270:16167–75
  • Zhang X, Song J, Shi X, et al. Absorption and metabolism characteristics of rutin in Caco-2 cells. Scientific World J 2013;10:382350
  • Floyd KA, Stella DR, Wang CC, et al. Genistein and genistein-containing dietary supplements accelerate the early stages of cataractogenesis in the male ICR/f rat. Exp Eye Res 2011;92:120–7
  • Nakatsuma A, Fukami T, Suzuki T, et al. Effects of kaempferol on the mechanisms of drug resistance in the human glioblastoma cell line T98G. Pharmazie 2010;65:379–83
  • Zhang S, Morris ME. Effect of the flavonoids biochanin A and silymarin on the P-glycoprotein-mediated transport of digoxin and vinblastine in human intestinal Caco-2 cells. Pharm Res 2003;20:1184–91
  • Pick A, Muller H, Mayer R, et al. Structure-activity relationships of flavonoids as inhibitors of breast cancer resistance protein (BCRP). Bioorg Med Chem 2011;19:2090–102
  • Srinivas NR. Recent trends in preclinical drug-drug interaction studies of flavonoids -Review of case studies, issues and perspectives. Phytother Res 2015;29:1679–91
  • Ma Y, Zeng M, Sun R, et al. Disposition of flavonoids impacts their efficacy and safety. Curr Drug Metab 2014;15:841–64
  • Actis-Goretta L, Lévèques A, Rein M, et al. Intestinal absorption, metabolism, and excretion of (-)-epicatechin in healthy humans assessed by using an intestinal perfusion technique. Am J Clin Nutr 2013;98:924–33
  • Yang Z, Kulkarni K, Zhu W, et al. Bioavailability and pharmacokinetics of genistein: mechanistic studies on its ADME. Anticancer Agents Med Chem 2012;12:1264–80
  • Qiu S, Sun H, Zhang AH, et al. Natural alkaloids: basic aspects, biological roles, and future perspectives. Chin J Nat Med 2014;12:401–6
  • Lei Y, Tan J, Wink M, et al. An isoquinoline alkaloid from the Chinese herbal plant Corydalis yanhusuo W.T. Wang inhibits P-glycoprotein and multidrug resistance-associate protein 1. Food Chem 2013;136:1117–21
  • Ma Y, Wink M. Lobeline, a piperidine alkaloid from Lobelia can reverse P-gp dependent multidrug resistance in tumor cells. Phytomedicine 2008;15:754–8
  • Chavez D, Cui B, Chai HB, et al. Reversal of multidrug resistance by tropane alkaloids from the stems of Erythroxylum rotundifolium. J Nat Prod 2002;65:606–10
  • Ikeda R, Che XF, Yamaguchi T, et al. Cepharanthine potently enhances the sensitivity of anticancer agents in K562 cells. Cancer Sci 2005;96:372–6
  • Wang YH, Goto M, Wang LT, et al. Multidrug resistance-selective antiproliferative activity of Piper amide alkaloids and synthetic analogues. Bioorg Med Chem Lett 2014;24:4818–21
  • Choi SU, Park SH, Kim KH, et al. The bisbenzylisoquinoline alkaloids, tetrandine and fangchinoline, enhance the cytotoxicity of multidrug resistance-related drugs via modulation of P-glycoprotein. Anticancer Drugs 1998;9:255–61
  • Arora A, Seth K, Kalra N, et al. Modulation of P-glycoprotein-mediated multidrug resistance in K562 leukemic cells by indole-3-carbinol. Toxicol Appl Pharmacol 2005;202:237–43
  • Mi Q, Cui B, Silva GL, et al. Pervilleines B and C, new tropane alkaloid aromatic esters that reverse the multidrug-resistance in the hollow fiber assay. Cancer Lett 2002;184:13–20
  • Chanmahasathien W, Ohnuma S, Ambudkar SV, et al. Biochemical mechanism of modulation of human P-glycoprotein by stemofoline. Planta Med 2011;77:1990–5
  • Shiraishi N, Akiyama S, Nakagawa M, et al. Effect of bisbenzylisoquinoline (biscoclaurine) alkaloids on multidrug resistance in KB human cancer cells. Cancer Res 1987;47:2413–16
  • Weiss J, Sauer A, Frank A, et al. Extracts and kavalactones of Piper methysticum G. Forst (kava-kava) inhibit P-glycoprotein in vitro. Drug Metab Dispos 2005;33:1580–3
  • Sun YF, Wink M. Tetrandrine and fangchinoline, bisbenzylisoquinoline alkaloids from Stephania tetrandra can reverse multidrug resistance by inhibiting P-glycoprotein activity in multidrug resistant human cancer cells. Phytomedicine 2014;21:1110–19
  • Chanmahasathien W, Ampasavate C, Greger H, et al. Stemona alkaloids, from traditional Thai medicine, increase chemosensitivity via P-glycoprotein-mediated multidrug resistance. Phytomedicine 2011;18:199–204
  • Egan D, O’Kennedy R, Moran E, et al. The pharmacology, metabolism, analysis and applications of coumarin and coumarin-related compounds. Drug Metab Rev 1990;22:503–29
  • Lacy A, O'Kennedy R. Studies on coumarins and coumarin-related compounds to determine their therapeutic role in the treatment of cancer. Curr Pharm Des 2004;10:3797–811
  • Raad I, Terreux R, Richomme P, et al. Structure-activity relationship of natural and synthetic coumarins inhibiting the multidrug transporter P-glycoprotein. Bioorg Med Chem 2006;14:6979–87
  • Barthomeuf C, Demeule M, Grassi J, et al. Conferone from Ferula schtschurowskiana enhances vinblastine cytotoxicity in MDCK-MDR1 cells by competitively inhibiting P-glycoprotein transport. Planta Med 2006;72:634–9
  • Barthomeuf C, Grassi J, Demeule M, et al. Inhibition of P-glycoprotein transport function and reversion of MDR1 multidrug resistance by cnidiadin. Cancer Chemother Pharmacol 2005;56:173–81
  • Bayet C, Fazio C, Darbour N, et al. Modulation of P-glycoprotein activity by acridones and coumarins from Citrus sinensis. Phytother Res 2007;21:386–90
  • Madureira AM, Molnar A, Abreu PM, et al. A new sesquiterpene-coumarin ether and a new abietane diterpene and their effects as inhibitors of P-glycoprotein. Planta Med 2004;70:828–33
  • Hanafi-Bojd MY, Iranshahi M, Mosaffa F, et al. Farnesiferol A from Ferula persica and galbanic acid from Ferula szowitsiana inhibit P-glycoprotein-mediated rhodamine efflux in breast cancer cell lines. Planta Med 2011;77:1590–3
  • Kimura S, Ito C, Jyoko N, et al. Inhibition of leukemic cell growth by a novel anti-cancer drug (GUT-70) from Calophyllum brasiliense that acts by induction of apoptosis. Int J Cancer 2005;113:158–65
  • Jabeen I, Wetwitayaklung P, Chiba P, et al. 2D- and 3D-QSAR studies of a series of benzopyranes and benzopyrano[3,4b][1,4]-oxazines as inhibitors of the multidrug transporter P-glycoprotein. J Comput Aided Mol Des 2013;27:161–71
  • Hoult JR, Payá M. Pharmacological and biochemical actions of simple coumarins: natural products with therapeutic potential. Gen Pharmacol 1996;27:713–22
  • Dewick PM. The biosynthesis of C5-C25 terpenoid compounds. Nat Prod Rep 2002;19:181–222
  • Yoshida N, Koizumi M, Adachi I, et al. Inhibition of P-glycoprotein-mediated transport by terpenoids contained in herbal medicines and natural products. Food Chem Toxicol 2006;44:2033–9
  • Appendino G, Jakupovic S, Tron GC, et al. Macrocyclic diterpenoids from Euphorbia semiperfoliata. J Nat Prod 1998;61:749–56
  • Valente I, Reis M, Duarte N, et al. Jatrophane diterpenes from Euphorbia mellifera and their activity as P-glycoprotein modulators on multidrug-resistant mouse lymphoma and human colon adenocarcinoma cells. J Nat Prod 2012;75:1915–21
  • Appendino G, Della Porta C, Conseil G, et al. A new P-glycoprotein inhibitor from the caper spurge (Euphorbia lathyris). J Nat Prod 2003;66:140–2
  • Madureira AM, Gyemant N, Ascenso JR, et al. Euphoportlandols A and B, tetracylic diterpene polyesters from Euphorbia portlandica and their anti-MDR effects in cancer cells. J Nat Prod 2006;69:950–3
  • Min YD, Kwon HC, Yang MC, et al. Isolation of limonoids and alkaloids from Phellodendron amurense and their multidrug resistance (MDR) reversal activity. Arch Pharm Res 2007;30:58–63
  • Lota ML, de Rocca Serra D, Tomi F, et al. Volatile components of peel and leaf oils of lemon and lime species. J Agric Food Chem 2002;50:796–805
  • Kawakami J, Yamamura Y, Santa T, et al. Kinetic analysis of glycyrrhetic acid, an active metabolite of glycyrrhizin, in rats: role of enterohepatic circulation. J Pharm Sci 1993;82:301–5
  • Reyes CP, Munoz-Martinez F, Torrecillas IR, et al. Biological evaluation, structure-activity relationships, and three-dimensional quantitative structure-activity relationship studies of dihydro-beta-agarofuran sesquiterpenes as modulators of P-glycoprotein-dependent multidrug resistance. J Med Chem 2007;50:4808–17
  • Molnar J, Gyemant N, Tanaka M, et al. Inhibition of multidrug resistance of cancer cells by natural diterpenes, triterpenes and carotenoids. Curr Pharm Des 2006;12:287–311
  • Fang S, Hao C, Sun W, et al. Rapid analysis of steroidal saponin mixture using electrospray ionization mass spectrometry combined with sequential tandem mass spectrometry. Rapid Commun Mass Spectrom Commun 1998;12:589–94
  • Yang Y, Laval S, Yu B. Chemical synthesis of saponins. Adv Carbohydr Chem Biochem 2014;71:137–226
  • D'Uva G, Lauriola M. Towards the emerging crosstalk: ERBB family and steroid hormones. Semin Cell Dev Biol 2015;12:250–5
  • Li Y, Fan L, Sun Y, et al. Paris saponin VII from trillium tschonoskii reverses multidrug resistance of adriamycin-resistant MCF-7/ADR cells via P-glycoprotein inhibition and apoptosis augmentation. J Ethnopharmacol 2014;154:728–34
  • Kim SW, Kwon HY, Chi DW, et al. Reversal of P-glycoprotein-mediated multidrug resistance by ginsenoside Rg(3). Biochem Pharmacol 2003;65:75–82
  • Choi CH, Kang G, Min YD. Reversal of P-glycoprotein-mediated multidrug resistance by protopanaxatriol ginsenosides from Korean red ginseng. Planta Med 2003;69:235–40
  • Nguyen VT, Darbour N, Bayet C, et al. Selective modulation of P-glycoprotein activity by steroidal saponines from Paris polyphylla. Fitoterapia 2009;80:39–42
  • Sun H, Yang Z, Ye Y. Structure and biological activity of protopanaxatriol-type saponins from the roots of Panax notoginseng. Int Immunopharmacol 2006;6:14–25
  • Wang Y, Zhang Y, Zhu Z, et al. Exploration of the correlation between the structure, hemolytic activity, and cytotoxicity of steroid saponins. Bioorg Med Chem 2007;15:2528–32
  • Loo TW, Bartlett MC, Clarke DM. Transmembrane segment 7 of human P-glycoprotein forms part of the drug-binding pocket. Biochem J 2006;399:351–9
  • Tan W, Mei H, Chao L, et al. Combined QSAR and molecule docking studies on predicting P-glycoprotein inhibitors. J Comput Aided Mol Des 2013;27:1067–73
  • Kim KH. 3D-QSAR analysis of 2,4,5- and 2,3,4,5-substituted imidazoles as potent and nontoxic modulators of P-glycoprotein mediated MDR. Bioorg Med Chem 2001;9:1517–23
  • Palmeira A, Sousa E, Vasconcelos MH, et al. Structure and ligand-based design of P-glycoprotein inhibitors: a historical perspective. Curr Pharm Des 2012;18:4197–214
  • Loo TW, Clarke DM. Identification of residues within the drug-binding domain of the human multidrug resistance P-glycoprotein by cysteine-scanning mutagenesis and reaction with dibromobimane. J Biol Chem 2000;275:39272–8

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.