Journal of Pharmaceutical Investigation

The Korean Society of Pharmaceutical Sciences and Technology (한국약제학회)
권호 표지
DOI QR코드

DOI QR Code

Effect of Natural Compounds on P-glycoprotein Activity in Human Uterine Sarcoma Cells

인체 자궁암 세포에서 천연 성분이 P-당단백질의 활성에 미치는 영향

  • 정수연 (이화여자대학교 약학대학) ;
  • 고은정 (이화여자대학교 약학대학) ;
  • 김나형 (이화여자대학교 약학대학) ;
  • 성민경 (이화여자대학교 약학대학) ;
  • 장정옥 (이화여자대학교 약학대학) ;
  • 이화정 (이화여자대학교 약학대학)
  • Published : 2005.08.20
Download PDF
⟨ Previous Next ⟩

Abstract

Multidrug resistance (MDR) of cancer cells is, at least in part, associated with the overexpression of P-glycoprotein (P-gp). Many studies have demonstrated that natural compounds obtained from fruits, vegetables, teas and medicinal plants may modulate P-gp activity. The objective of the present investigation was to examine the effect of seven natural compounds on the P-gp activity in human uterine sarcoma cell line, MES-SA/DX5. Daunomycin uptake was significantly increased by biochanin A and silymarin (p<0.0001) whereas it was reduced by morin (p<0.01). The efflux of daunomycin from the cells was significantly inhibited by biochanin A, morin, cephalotaxine, berberine (p<0.05) and silymarin (p<0.0001). Biochanin A, berberine and silymarin significantly decreased $IC_{50}$ value of daunomycin (p<0.05) while morin increased it (p<0.05). These results suggest that some natural compounds such as biochanin A and silymarin may inhibit P-gp function and can be developed as MDR reversing agents to improve the efficacy of chemotherapeutic drugs when administered concomitantly.

Keywords

References

  1. P.F. Juranka, R.I. Zastawny and V. Ling, P-glycoprotein multidrug resistance and a superfamily of membraneassociated transport proteins, FASEB J., 3, 2583-2592 (1989) https://doi.org/10.1096/fasebj.3.14.2574119
  2. S.A.W. Fuqua, I.M. Moretti-Rojas, S.L. Schneider and W.L. McGuire, P-glycoprotein expression in human breast cancer cells, Cancer Res., 47, 2103-2106 (1987)
  3. J.A. Endicott and V. Ling, The biochemistry of Pglycoprotein-mediated multidrug resistance, Ann. Rev. Biochem., 58, 137-171 (1989) https://doi.org/10.1146/annurev.bi.58.070189.001033
  4. M.M. Gottesman and I. Pasran, Biochemistry of multi drug resistance mediated by the multidrug transporter, Ann. Rev. Biochem., 62, 385-427 (1993) https://doi.org/10.1146/annurev.bi.62.070193.002125
  5. F. Theibaut, T. Tsuruo, H. Hamada, M.M. Gottesman, I. Pastan and M.C. Willingham, Localization of the multidrug resistance gene product P-glycoprotein in normal human tissues, Proc. Natl. Acad. Sci., 84,7735-7738 (1987)
  6. B.L. Lum and M.P. Gosland, MDR expression in normal tissues. Pharmacologic implications for the clinical use of P-glycoprotein inhibitors. Hematol. Oncol. Clin. North Am., 9, 319-336 (1995)
  7. M.F. Fromm, P-glycoprotein: A defense mechanism limiting oral bioavailability and CNS accumulation of drug, Int. J. Clin. Pharmacol. Ther., 38, 69-74 (2000) https://doi.org/10.5414/CPP38069
  8. R.W. Stenkampf and W.D. Klohs, Possible link between the intrinsic drug resistance of colon tumor and a detoxification mechanism of intestinal cell, Cancer Res., 48, 3025-3030 (1988)
  9. J.M. Phang, C.M. Poore, J. Lopaczynska and G.C. Yeh, Flavol-stimulated efflux of 7,12-dimethylbenz(${\alpha}$)anthracene in multidrug-resistant breast cancer cells. Cancer Res., 53, 5977-5981 (1993)
  10. T. Ikegawa, H. Ohtani, N. Koyabu, M. Juichi, Y Iwase, C. Ito, H. Furukawa, M. Naito, T. Tsuruo and Y. Sawada, Inhibition of P-glycoprotein by flavonoid derivatives in adriamycin-resistant human myelogenous leukemia (K562/ADM) cell, Cancer lett., 177, 89-93 (2002) https://doi.org/10.1016/S0304-3835(01)00761-3
  11. G. Scambia, F.O. Ranelleti, P.B. Panici, R. DiVincenzo, G. Bonanno, G. Ferrandina, M. Piantelli, S. Bussa, C. Rumi, M. Cianfriglia and S. Mancuso, Quercetin potentiates the effect of adriamycin in a multidrug-resistant MCF-7 human breast cancer cell line: P-glycoprotein as a possible target, Cancer Chemother. Pharmacol., 34, 459-464 (1994) https://doi.org/10.1007/BF00685655
  12. E. Chieli, N. Romiti, F. Cervelli and R. Tongiani, Effects of flavonols on P-glycoprotein activity in cultured rat hepatocytes, Life Sci., 57, 1741-1751 (1995) https://doi.org/10.1016/0024-3205(95)02152-9
  13. J.W. Critchfield, C.J. Welsh, J.M. Phang and G.C. Yeh, Modulation of adriamycin accumulation and efflux by flavonoids in HCT-15 colon cells: activation of P-glycoprotein as a putative mechanisms, Biochem. Pharmacol., 48, 1437-1445 (1994) https://doi.org/10.1016/0006-2952(94)90568-1
  14. G.C. Yeh, J. Lopaczynska, C.M. Poore and J.M. Phang, A new functional role for P-glycoprotein: Efflux pump for benzo[${\alpha}$]pyrene in human breast cancer MCF-7 cells, Cancer Res., 52, 6692-6695 (1992)
  15. T. Efferth, M. Davey, A. Olbrich, G. Rucker, E. Gebhart and R. Davey, 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 (2002) https://doi.org/10.1006/bcmd.2002.0492
  16. N.P. Singh and H. Lai, Selective toxicity of dihydroartemisinin and holotransferrin toward human breast cancer cells, Life Sei., 70,49-56 (2001) https://doi.org/10.1016/S0024-3205(01)01372-8
  17. T. Efferth, H. Dunstan, A. Sauerbrey, H. Miyachi and C.R. Chitambar, The anti-malarial artesunate is also active against cancer, Int. J. Oncol., 18, 767-773 (2001)
  18. H. Saloniemi, K. Wahala, P. Nykanen-kurki, K. Kallela and I. Saastamoinen, Phytoestrogen content and estrogenic effect of legume fodder, Pros. Soc. Exp. Biol, Med., 208, 13-17 (1995) https://doi.org/10.3181/00379727-208-43825
  19. Y.S. Lee, T.H. Kim, K.J. Cho and J.J. Jang, Inhibitory effects of biochanin A on benzo[${\alpha}$]pyrene induced carcinogenesis in mice, In vivo, 6, 283-286 (1992)
  20. T. Gotoh, K. Yamada, H. Yin, A. Ito, T. Kataoka and K. Dohi, Chemoprevention of N-nitroso-N-methylurea-induced rat manunary carcinogenesis by soy foods or biochanin A. Jpn. J. Cancer Res., 89, 137-142 (1998) https://doi.org/10.1111/j.1349-7006.1998.tb00541.x
  21. W.M. Keung, O. Lazo, L. Kunze and B.L. Vallee, Potentiation of the bioavailability of daidzein by an extract of Radix puerariae, Proc. Natl. Acad Sci. USA, 93, 4284-4288 (1996)
  22. W.M. Keung, O. Lazo, L. Kunze and B.L. Vallee, Daidzein suppresses ethanol consumption by Syrian golden hamsters without blocking acetaldehyde metabolism, Proc. Natl. Acad Sci. USA, 92, 8990-8993 (1995)
  23. I.M. Liu and S.J. Sheu, Analysis and processing of Chinese herbal drugs. VIII: The study of sophorae floe. Am. J. Chin. Med, 17, 179-87 (1989) https://doi.org/10.1142/S0192415X89000279
  24. V. Elangovan, N. Sekar and S. Govindasamy, Chemopreventive potential of dietary bioflavonoids against 20-methylcholanthrene-induced tumorigenesis, Cancer Lett., 87, 107-13 (1994) https://doi.org/10.1016/0304-3835(94)90416-2
  25. T. Tanaka, K. Kawabata, S. Honjo, Tanaka T., H. Kohno, M. Murakami, R Shimada, K. Matsunaga, Y. Yamada and M. Shimizu, Inhibition of azoxymethane-induced aberrant crypt foci in rats by natural compounqs, caffeine, quercetin and morin, Oncol. Rep., 6, 1335-40 (1999)
  26. R.P. Singh and R. Agarwal, Prostate cancer prevention by silibirin, Curr. Cancer Drug Targets, 4, 1-11 (2004) https://doi.org/10.2174/1568009043481605
  27. K. Kropachova and E. Mishurova, Flavobion and thioctacid lessen irradiation-induced latent injury of the liver, Biull. Eksp. Bioi. Med, 113, 547-549 (1992)
  28. M. Velussi, A.M. Cemigoi, A De Monte, F. Dapas, C. Caffau and M. Zilli, Long-term (12 months) treatment with an anti-oxidant drug (silymarin) is effective on hyperinsulinemia, exogenous insulin need and malondialdehyde levels in cirrhotic diabetic patients, J. Hepatol., 26, 4871-4879 (1997)
  29. T. Efferth, A Sauerbrey, M.E. Halatsch, D.D. Ross and E. Gebhart, Molecular modes of action of cephalotaxine and homoharringtorrine from the coniferous tree Cephalotaxus hainanensis in human tumor cell lines, Naunyn Schmiedebergs Arch. Pharmacol., 367, 56-67 (2002)
  30. A.H. Amin, T.V. Subbaiah and K.M. Abbasi, Berberine sulfate: antimicrobial activity, bioassay, and mode of action, Can. J. Microbiol., 15, 1067-76 (1969) https://doi.org/10.1139/m69-190
  31. W.G. Harker, E.R. Mackintosh and B.I. Sikic, Development and characterization of a human sarcoma cell line, MES-SA, sensitive to multiple drug, Cancer Res., 43, 4943-4950 (1983)
  32. G. Harker and B.I. Sikic, Multidrug (pleiotropic) resistance in doxorubicin-selected variants of the human sarcoma cell line MES-SA, Cancer Res., 45, 4091-4096 (1985)
  33. E.J. Go, S.Y. Chung, N.H. Kim and H.J. Lee, Modulation of P-glycoprotein activity by flavonoids in human uterine sarcoma cells, J. Kor. Pharm. Sci., 33, 305-310 (2003)
  34. S.Y. Chung, E.J. Go, N.H. Kim and H.J. Lee, Effect of flavonoids on efflux and cytotoxicity of daunomycin, J. Kor. Pharm. Sci., 34, 95-99 (2004)
  35. P. Skehan, R. Storeng, D. Scudiero, A. Monks, J. McMahon, D. Vistica, J.T. Warren, H. Bokesch, S. Kenny and M.R. Boyd, New colorimetric cytotoxicity assay for anticancerdrug screening, J. Natl. Cancer. Inst., 82, 1107-1112 (1990) https://doi.org/10.1093/jnci/82.13.1107
  36. S. Zhang and M.E. Morris, Effects of the flavonoids biochanin A, morin, phloretin, and silymarin on P-glycoprotein-mediated transport, J. Pharmacol. Exp. Ther., 304, 1258-1267 (2003) https://doi.org/10.1124/jpet.102.044412
  37. L. Movileanu, I. Neagoe and M.L. Flonta, Interation of the antioxidant flavonoid quercetin with planar lipid bilayers, Int. J. Pharm., 205, 135-146 (2000) https://doi.org/10.1016/S0378-5173(00)00503-2
  38. V.J. Wacher, L. Salphati and L.Z. Benet, Active secretion and enterocyte drug metabolism barriers to drug absorption. Adv. Drug Del. Rev., 20, 99-112 (1996) https://doi.org/10.1016/0169-409X(95)00127-S