Abstract
P-Glycoprotein (P-gp), an ATP-binding cassette transporter, plays an important role in multidrug resistance (MDR). α-Asarone and β-asarone, bioactive cis–trans isomers found in Acorus tatarinowii Schott, were tested for their potential ability to modulate the expression and function of P-gp in Caco-2 cells. MTT assays revealed that both α-asarone and β-asarone significantly enhanced the vincristine-induced cytotoxicity to cells. β-Asarone was the most potent. Flow cytometry showed that α- and β-asarone increased Rhodamine 123 (Rh123) uptake and inhibited Rh123 efflux in Caco-2 cells in a concentration-dependent manner. Furthermore, P-gp expression and P-gp mRNA in cells were decreased by exposure to α- and β-asarone. In addition, β-asarone increased the inhibition of P-gp activity in cells more than α-asarone. Thus, α- and β-asarone effectively reversed MDR by inhibiting P-gp function and expression.
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References
Chaudhary PM, Mechetner EB, Roninson IB (1992) Expression and activity of the multidrug resistance P-glycoprotein in human peripheral blood lymphocytes. Blood 80:2735–2739
Chen H, Li WG, Zhang XB, Wang L, Xu TL, Wu DZ, Li Y (2013) Alpha-asarone from Acorus gramineus alleviates epilepsy by modulating A-type gaba receptors. Neuropharmacology 65:1–11
Dandiya PC, Menon MK (1964) Actions of asarone on behavior, stress, and hyperpyrexia, and its interactions with central stimulants. J Pharmacol Exp Ther 145:42–46
Fromm MF, Kim RB, Stein CM, Wilkinson GR, Roden DM (1999) Inhibition of P-glycoprotein-mediated drug transport: a unifying mechanism to explain the interaction between digoxin and quinidine. Circulation 99:552–557
Garduno L, Salazar M, Salazar S, Morelos ME, Labarrios F, Tamariz J, Chamorro GA (1997) Hypolipidaemic activity of α-asarone in mice. J Ethnopharmacol 55:161–163
Green LJ, Marder P, Slapak CA (2001) Modulation by LY335979 of P-glycoprotein function in multidrug-resistant cell lines and human natural killer cells. Biochem Pharmacol 61:1393–1399
Ito S, Woodland C, Harper PA, Koren G (1993) The mechanism of the verapamil–digoxin interaction in renal tubular cells (LLC-PK1). Life Sci 53:399–403
Juliano RL (1976) The role of drug delivery systems in cancer chemotherapy. Prog Clin Biol Res 9:21–32
Lee B, Choi Y, Kim H, Kim SY, Hahm DH, Lee HJ, Shim I (2003) Protective effects of methanol extract of Acori graminei rhizoma and Uncariae ramulus et Uncus on ischemia-induced neuronal death and cognitive impairments in the rat. Life Sci 74:435–450
Liu J, Li C, Xing G, Zhou L, Dong M, Geng Y, Li X, Li J, Wang G, Zou D, Niu Y (2010) Beta-asarone attenuates neuronal apoptosis induced by beta amyloid in rat hippocampus. Yakugaku Zasshi 130:737–746
Lucia MB, Cauda R, Landay AL, Malorni W, Donelli G, Ortona L (1995) Transmembrane P-glycoprotein (P-gp/P-170) in HIV infection: analysis of lymphocyte surface expression and drug-unrelated function. AIDS Res Hum Retrovir 11:893–901
Okamura N, Hirai M, Tanigawara Y, Tanaka K, Yasuhara M, Ueda K, Komano T, Hori R (1993) Digoxin–cyclosporin A interaction: modulation of the multidrug transporter P-glycoprotein in the kidney. J Pharmacol Exp Ther 266:1614–1619
Tan B, Piwnica-Worms D, Ratner L (2000) Multidrug resistance transporters and modulation. Curr Opin Oncol 12:450–458
Wang EJ, Casciano CN, Clement RP, Johnson WW (2001) Active transport of fluorescent P-glycoprotein substrates: evaluation as markers and interaction with inhibitors. Biochem Biophys Res Commun 289:580–585
Wu QD, Fang YQ, Chen YZ, Kuan ZS, Wang SY, He YP (2005) Protective eEffects of volatile oil of Acorus tatarinowii Schott and β-asarone on cardiovascular system. Tradit Chin Drug Res Clin Pharmacol 4:244–247
Yang K, Wu J, Li X (2008) Recent advances in the research of P-glycoprotein inhibitors. Biosci Trends 2:137–146
Yang Y, Wang SX, Fang MF, Yang LJ, Meng X, Zheng XH (2012) Modulation of P-glycoprotein by benzaldehyde, vanillin and β-asarone. Chin Tradit Pat Med 7:1364–1366
Zamora JM, Pearce HL, Beck WT (1988) Physical–chemical properties shared by compounds that modulate multidrug resistance in human leukemia cells. Mol Pharmacol 33:454–462
Zuo HL, Yang FQ, Zhang XM, Xia ZN (2011) Separation of cis-and trans-asarone from Acorus tatarinowii by preparative gas chromatography. J Anal Methods Chem 2012:1–5
Acknowledgments
This work was supported by Education, Science, and Technology Development Center (IRT1174); Ministry of Science and Technology of the People’s Republic of China (No. 2008BAI51B01); Science, Industry, Trade and Information Technology Commission of Shenzhen Municipality, China (JC201005280632A, CXB201005260069A); and National Natural Science Foundation of China (No. 21005060).
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Meng, X., Liao, S., Wang, X. et al. Reversing P-glycoprotein-mediated multidrug resistance in vitro by α-asarone and β-asarone, bioactive cis–trans isomers from Acorus tatarinowii . Biotechnol Lett 36, 685–691 (2014). https://doi.org/10.1007/s10529-013-1419-8
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DOI: https://doi.org/10.1007/s10529-013-1419-8