Inhibitory of the Human Cytochrome P450 2A6 and Cytochrome P450 2A13 by Ginger Extracts and Starfruits Extracts
Abstract
The liver specific cytochrome P450 2A6 and the lung-specific 2A13 enzyme has been shown to associate with smoking behavior and adenocarcinoma lung cancer rate in smokers. Therefore, inhibition of these two enzymes by specific inhibitor could be an aid in smoking cession and lung cancer prevention. Our preliminary studied indicated that the ginger and starfruits juices could potently inhibit the CYP2A6 and CYP2A13 enzyme. In this study, both plant extracts could inhibit both enzymes in an irreversible mode in which the inhibition depends on the NADPH-, time-, and concentration of inhibitor. Ethyl acetate fraction of starfruits extract could inhibit CYP2A6 and CYP2A13 enzymes with an IC50 of 8.82± 0.23 µg/ml and 20.44 ± 0.16 µg/ml, respectively. Similarly, the ethyl acetate fraction of the ginger extract could inhibit CYP2A6 and CYP2A13 enzymes with an IC50 of 1.80± 0.07µg/ml and 11.81± 0.18 µg/ml, respectively. Keywords : Cytochrome P450 2A6 and 2A13, irreversible inhibitionReferences
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Schlicht, K.E., Berg, J.Z., Murphy, S.E. (2009). Effect of CYP2A13 Active Site Mutation N297A on Metabolism of Coumarin and Tobacco-Specific Nitrosamines. Drug metabolism and Disposition, 37, 665–671.
Shen, A.L., Porter, T.D., Wilson, T.E., Kasper, C.B. (1989). Structural Analysis of the FMN Binding Domain of NADPHCytochrome P-450 Oxidoreductase by Site-directed Mutagenesis. Journal of Biological Chemistry, 264, 7584-7589.
Zhang, J.W., Liu, Y., Cheng, J., Li, W., Ma, H., Liu, H.T., Sun, J., Wang, L.M., He, Y.Q., Wang, Y., Wang, Z.T., Yang, L. (2007). Inhibition of human liver cytochrome P450 by star fruit juice. Journal of Pharmacology and Pharmaceutical Science, 10 (4), 496-
Guo, L.Q., Fukuda, K., Ohta, T., Yamazoe, Y. (2000) Role of furanocoumarin derivatives on grapefruit juice –
mediated inhibition of human CYP3A activity. Drug Metabolism and Disposition, 28(7), 766-771.
Hecht, S.S. (1998). Biochemistry, biology, and carcinogenicity of tobacco-specific Nnitrosamines. Chemical Research in Toxicology, 11, 559-603.
Hukkanen, J., Jacob, P., Benowitz, N.L. (2005). Metabolism and disposition kinetics of nicotine. Pharmacological Reviews, 57(1), 79-115.
Li., S, Xiaoli, F. (2013). Expression of cytochrome P450 2A13 in human non-small cell lung cancer and its clinical significance. The Journal of Biomedical Research, 27(3), 202-207.
Ortiz de Montellano, P.R. (Ed.) (2005). Cytochrome P450: Structure, Mechanism and Biochemistry,
third edition. New York: Kluwer Academic/Plenum Publishers.
Patten, C.J., Smith, T.J., Murphy, S.E., Wang, M.H., Lee, J., Tynes, R.E., Koch, P., Yang, C.S. (1996).Kinetic analysis of the activation of 4-(methylnitrosamino )-1-(3-pyridyl)-1-butanone by heterologous expressed human P450 enzymes and the effect of P450-specific chemical inhibitors on this activation in human liver microsomes. Archives of Biochemistry and Biophysics, 333, 127-138.
Pouyfung, P., Prasopthum, A., Sarapusit, S., Srisook, E., Rongnoparut, P. (2014). Mechanism-based inactivation of cytochrome P450 2A6 and 2A13 by Rhinacanthus nasutus constituents. Drug Metabolism and Phamacokinetics, 29(1), 75-82.
Schlicht, K.E., Berg, J.Z., Murphy, S.E. (2009). Effect of CYP2A13 Active Site Mutation N297A on Metabolism of Coumarin and Tobacco-Specific Nitrosamines. Drug metabolism and Disposition, 37, 665–671.
Shen, A.L., Porter, T.D., Wilson, T.E., Kasper, C.B. (1989). Structural Analysis of the FMN Binding Domain of NADPHCytochrome P-450 Oxidoreductase by Site-directed Mutagenesis. Journal of Biological Chemistry, 264, 7584-7589.
Zhang, J.W., Liu, Y., Cheng, J., Li, W., Ma, H., Liu, H.T., Sun, J., Wang, L.M., He, Y.Q., Wang, Y., Wang, Z.T., Yang, L. (2007). Inhibition of human liver cytochrome P450 by star fruit juice. Journal of Pharmacology and Pharmaceutical Science, 10 (4), 496-
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2017-07-19
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บทความวิจัยจากการประชุมวิชาการระดับชาติ"วิทยาศาสตร์วิจัย"ครั้งที่ 9
