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Modulatory Effects of Natural Curcuminoids on P-Glycoprotein ATPase of Insecticide-Resistant Pest Helicoverpa armigera (Lepidopetera: Noctüidae)

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Abstract

Three major curcuminoids (I, II and III) were purified from turmeric and tested for their ability to modulate the function of P-glycoprotein ATPase of the insecticide-resistant pest Helicoverpa armigera (Ha-Pgp). The curcumin mixture inhibited the activity of Ha-Pgp ATPase by 80–90% at 100 μM concentration. Along with curcuminoids I, II and III, it inhibited the verapamil- and ethylparaoxon-stimulated Ha-Pgp ATPase activity. Curcuminoid binding was quantitated by quenching the intrinsic Trp fluorescence of purified Ha-Pgp ATPase. Transport was monitored in proteoliposomes containing Ha-Pgp ATPase using the high-affinity fluorescent substrate tetramethylrosamine (TMR) in real time. Addition of the curcuminoid mixture collapsed the TMR concentration gradient generated by Ha-Pgp ATPase. Inhibition studies on Ha-Pgp ATPase activity are important to develop strategies to overcome insecticide resistance in this pest.

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References

  • Abu-Qare AW, Elmasry E, Abou-Donia MB (2003) A role for P-glycoprotein in environmental toxicology. J Toxicol Environ Health B Crit Rev 6:279–288

    Article  CAS  PubMed  Google Scholar 

  • Anuchapreeda S, Leechanachai P, Smith M, Ambudkar SV, Limtrakul P (2002) Modulation of P-glycoprotein expression and function by curcumin in multidrug resistant human KB cells. Biochem Pharmacol 64:573–582

    Article  CAS  PubMed  Google Scholar 

  • Armes NJ, Jadhay DR, Bond GS, King ABS (1992) Insecticide resistance in Helicoverpa armigera in south India. Pestic Sci 34:355–364

    Article  CAS  Google Scholar 

  • Aurade R, Jayalakshmi SK, Sreeramulu K (2006) Stimulatory effect of insecticides on partially purified P-glycoprotein ATPase from the resistant pest Helicoverpa armigera. Biochem Cell Biol 84:1045–1050

    Article  CAS  PubMed  Google Scholar 

  • Aurade MR, Jayalakshmi SK, Sreeramulu K (2010) P-glycoprotein ATPase from the resistant pest, Helicoverpa armigera: purification, characterization and effect of various insecticides on its transport function. Biochem Biophys Acta 1798:1135–1143

    Article  CAS  PubMed  Google Scholar 

  • Borgnia MJ, Eytan GD, Assaraf YG (1996) Competition of hydrophobic peptides, cytotoxic drugs, and chemosensitizers on a common P-glycoprotein pharmacophore as revealed by its ATPase activity. J Biol Chem 271:3163–3171

    Article  CAS  PubMed  Google Scholar 

  • Boumendjel A, Di Pietro A, Dumontet C, Barron D (2002) Recent advances in the discovery of flavonoids and analogs with high-affinity binding to glycoprotein responsible for cancer cell multidrug resistance. Med Res Rev 22:512–529

    Article  CAS  PubMed  Google Scholar 

  • Chearwae W, Anuchapreeda S, Nandigama K, Ambudkar SV, Limtrakul P (2004) Biochemical mechanism of modulation of human P-glycoprotein (ABCB1) function by curcuminoids purified from turmeric powder. Biochem Pharmacol 68:2043–2052

    Article  CAS  PubMed  Google Scholar 

  • Chearwae W, Chung-Pu W, 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

    Article  CAS  PubMed  Google Scholar 

  • Conseil G, Baubichon-Cortay H, Dayan G, Jault JM, Barron D, DiPietro A (1998) Flavonoids: a class of modulators with bifunctional interactions at vicinal ATP and steroid-binding sites on mouse P-glycoprotein. Proc Natl Acad Sci USA 95:9831–9836

    Article  CAS  PubMed  Google Scholar 

  • Dassa E, Bouige P (2001) The ABC of ABCs: a phylogenetic and functional classification of ABC systems in living organisms. Res Microbiol 152:211–229

    Article  CAS  PubMed  Google Scholar 

  • Dong M, Penin F, Baggetto LG (1996) Efficient purification and reconstitution of P-glycoprotein for functional and structural studies. J Biol Chem 271:28875–28883

    Article  CAS  PubMed  Google Scholar 

  • Gottesman MM, Pastan I (1993) Biochemistry of multidrug resistance mediated by the multidrug transporter. Annu Rev Biochem 62:385–427

    Article  CAS  PubMed  Google Scholar 

  • Hemanta C, Suresh W, Saxena VS (2000) Isolation, characterization and insect growth inhibitory activity of major turmeric constituents and their derivatives against Schistocerca gregaria (Forsk) and Dysdercus koenigii (Walk). Pest Manag Sci 56:1086–1092

    Article  Google Scholar 

  • Hong J, Lambert JD, Lee SH, Sinko PJ, Yang CS (2003) Involvement of multidrug resistance associated proteins in regulating cellular levels of (–)epigallocatechin-3-gallate and its methyl metabolites. Biochem Biophys Res Commun 310:222–227

    Article  CAS  PubMed  Google Scholar 

  • Jones PM, George AM (2004) The ABC transporter structure and mechanism: perspectives on recent research. Cell Mol Life Sci 61:682–699

    Article  CAS  PubMed  Google Scholar 

  • Kranthi KR, Jadhav DR, Wanjari RR, Ali SS, Russell D (2001) Carbamate and organophosphate resistance in cotton pests in India, 1995 to 1999. Bull Entomol Res 91:37–46

    CAS  PubMed  Google Scholar 

  • Lanning CL, Fine RL, Corcoran JJ, Ayad HM, Rose RL, Abou-Donia MB (1996) Tobacco budworm P-glycoprotein: biochemical characterization and its involvement in pesticide resistance. Biochim Biophys Acta 1291:155–162

    PubMed  Google Scholar 

  • Leslie EM, Deeley RG, Cole SPC (2005) Multidrug resistance proteins: role of P-glycoprotein, MRP1, MRP2, and BCRP (ABCG2) in tissue defense. Toxicol Appl Pharmacol 204:216–237

    Article  CAS  PubMed  Google Scholar 

  • Limtrakul P, Chearwae W, Sukla S, Phisalphong C, Ambudkar SV (2007) 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. Mol Cell Biochem 296:85–95

    Article  CAS  PubMed  Google Scholar 

  • Locher KP (2004) Structure and mechanism of ABC transporters. Curr Opin Struct Biol 14:426–431

    Article  CAS  PubMed  Google Scholar 

  • Lu P, Liu R, Sharom FJ (2001) Drug transport by reconstituted P-glycoprotein in proteoliposomes—effect of substrates and modulators, and dependence on bilayer phase state. Eur J Biochem 268:1687–1697

    Article  CAS  PubMed  Google Scholar 

  • Mayer U, Wagenaar E, Dorobek B, Beijnen JH, Borst P, Schinkel AH (1997) Full blockage of intestinal P-glycoprotein by oral treatment of mice with PS833. J Clin Investig 100:2430–2436

    Article  CAS  PubMed  Google Scholar 

  • Prasad R, Murthy SK, Prasad R, Gupta V, Lata S (1996) Multidrug resistance: an emerging threat. Curr Sci 71:205–213

    CAS  Google Scholar 

  • Ramsewak RS, Dewitt DL, Nair MG (2000) Cytotoxicity, antioxidant and anti-inflammatory activities of curcumin I-III from Curcuma longa. Phytomedicine 7:303–308

    CAS  PubMed  Google Scholar 

  • Roth GN, Chandra A, Nair NG (1998) Novel bioactive of Curcuma longa constituents. J Nat Prod 61:542–545

    Article  CAS  PubMed  Google Scholar 

  • Sauna ZE, Ambudkar SV (2001) 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. J Biol Chem 276:11653–11661

    Article  CAS  PubMed  Google Scholar 

  • Sharom FJ (1997) The P-glycoprotein efflux pump: how does it transport drugs? J Membr Biol 160:161–175

    Article  CAS  PubMed  Google Scholar 

  • Sharom FJ, Yu X, Chu JWK, Doige CA (1995) Characterization of the ATPase activity of P-glycoprotein from multidrug-resistant Chinese hamster ovary cells. Biochem J 308:381–390

    CAS  PubMed  Google Scholar 

  • Sharom FJ, Liu RH, Romsicki Y (1998) Spectroscopic and biophysical approaches for studying the structure and function of the P-glycoprotein multidrug transporter. Biochem Cell Biol 76:695–708

    Article  CAS  PubMed  Google Scholar 

  • Sikic BI (1999) Modulation of multidrug resistance: a paradigm for translational clinical research. Oncology (Hunting) 13:183–187

    CAS  Google Scholar 

  • Solsoloy AD, Cacayorin ND, Cano LC (1991) Insecticidal and fungicidal action of some indigenous plant extracts against cotton pests. Cotton Res J (Philippines) 4:1–11

    Google Scholar 

  • Sreeramulu K, Liu R, Sharom FJ (2007) Interaction of insecticides with mammalian P-glycoprotein and their effect on its transport function. Biochim Biophys Acta 1768:1750–1757

    Article  CAS  PubMed  Google Scholar 

  • Srinivas R, Udikeri SS, Jayalakshmi SK, Sreeramulu K (2004) Identification of factors responsible for insecticide resistance in Helicoverpa armigera. Comp Biochem Physiol C Toxicol Pharmacol 137:261–269

    Article  CAS  PubMed  Google Scholar 

  • Srinivas R, Jayalakshmi SK, Sreeramulu K, Sherman NE, Rao J (2006) Purification and characterization of an esterase isozyme involved in hydrolysis of organophosphorus compounds from an insecticide resistant pest, Helicoverpa armigera (Lepidoptera: Noctüidae). Biochim Biophys Acta 1760:310–317

    CAS  PubMed  Google Scholar 

  • Suneet S, Zaher H, Anika H, Bauer B, Ware JA, Ambudkar SV (2009) Curcumin inhibits the activity of ABCG2/BCRP1, a multidrug resistance-linked ABC drug transporter in mice. Pharm Res 26:480–487

    Article  Google Scholar 

  • Tsuruo T, Lida H, Tsukagoshi S, Sakurai Y (1981) Overcoming of vincristine resistance in P388 leukemia in vivo and in vitro through enhanced cytotoxicity of vincristine and vinblastine by verapamil. Cancer Res 41:1967–1972

    CAS  PubMed  Google Scholar 

  • Twentyman PR, Bleehen N (1991) Resistance modification by PSC-833 a novel non-immunosuppressive cylosporin. Eur J Cancer 7:1639–1642

    Google Scholar 

  • Urbatsch IL, Sankaran B, Weber J, Senior AE (1995) P-glycoprotein is stably inhibited by vanadate-induced trapping of nucleotide at a single catalytic site. J Biol Chem 270:19383–19390

    Article  CAS  PubMed  Google Scholar 

  • Wortelboer HM, Usta M, Vandervelde AE, Boersma MG, Spenkelink B, Van Zanden JJ, Rietjens IM, Van Bladeren PJ, Cnubben NH (2003) Interplay between MRP inhibition and metabolism of MRP inhibitors: the case of curcumin. Chem Res Toxicol 16:1642–1651

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This research was supported by a research grant to K. S. from the Department of Science and Technology and SAP of the University Grant Commission, New Delhi, India. R. M. A. thanks the Council of Scientific and Industrial Research, New Delhi, India, for financial assistance in the form of SRF during this work.

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Correspondence to Kuruba Sreeramulu.

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Aurade, R.M., Jayalakshmi, S.K. & Sreeramulu, K. Modulatory Effects of Natural Curcuminoids on P-Glycoprotein ATPase of Insecticide-Resistant Pest Helicoverpa armigera (Lepidopetera: Noctüidae). J Membrane Biol 236, 271–278 (2010). https://doi.org/10.1007/s00232-010-9299-5

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