Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
권호 표지
DOI QR코드

DOI QR Code

Mechanism of Inhibition of Human Cytochrome P450 1A1 and 1B1 by Piceatannol

  • Published : 2008.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

The resveratrol analogue piceatannol (3,5,3',4'-tetrahydroxy-trans-stilbene) is a polyphenol present in grapes and wine and reported to have anti-carcinogenic activities. To investigate the mechanism of anticarcinogenic activities of piceatannol, the effects on CYP 1 enzymes were determined in Escherichia coli membranes coexpressing recombinant human CYP1A1, CYP1A2 or CYP1B1 with human NADPH-P450 reductase. Piceatannol showed a strong inhibition of CYP1A1 and CYP1B1 in a concentration-dependent manner, and $IC_{50}$ of human CYP1A1 and CYP1B1 was 5.8 ${\mu}M$ and 16.6 ${\mu}M$, respectively. However, piceatannol did not inhibit CYP1A2 activity in the concentration of up to 100 ${\mu}M$. Piceatannol exhibited 3-fold selectivity for CYP1B1 over CYP1A1. The mode of inhibition of piceatannol was non-competitive for CYP1A1 and CYP1B1. The result that piceatannol did not inhibit CYP1B1-mediated $\alpha$-naphthoflavone ($\alpha$-NF) metabolism suggests piceatannol may act as a non-competitive inhibitor as well. In human prostate carcinoma PC-3 cells, piceatannol induces apoptosis and prevents Aktmediated signal pathway. Taken together, abilities of piceatannol to induce apoptotic cell death as well as CYP1 enzyme inhibition make this compound a useful tool for cancer chemoprevention.

Keywords

References

  1. Altomare, D. A. and Testa, J. R. (2005). Perturbations of the AKT signaling pathway in human cancer. Oncogene 24, 7455-7464 https://doi.org/10.1038/sj.onc.1209085
  2. Aziz, M. H., Nihal, M., Fu, V. X., Jarrard, D. F. and Ahmad, N. (2006). Resveratrol-caused apoptosis of human prostate carcinoma LNCaP cells is mediated via modulation of phosphatidylinositol 3'-kinase/Akt pathway and Bcl-2 family proteins. Mol. Cancer Ther. 5, 1335-1341 https://doi.org/10.1158/1535-7163.MCT-05-0526
  3. Benistant, C., Chapuis, H. and Roche, S. (2000). A specific function for phosphatidylinositol 3-kinase alpha (p85 alphap110 alpha) in cell survival and for phosphatidylinositol 3- kinase beta (p85 α-p110 α) in de novo DNA synthesis of human colon carcinoma cells. Oncogene 19, 5083-5090 https://doi.org/10.1038/sj.onc.1203871
  4. Burke, M. D., Thompson, S., Elcombe, C. R., Halpert, J., Haaparanta, T. and Mayer, R. T. (1985). Ethoxy-, pentoxy- and benzyloxyphenoxazones and homologues: a series of substrates to distinguish between different induced cytochromes P-450. Biochem. Pharmacol. 34, 3337-3345 https://doi.org/10.1016/0006-2952(85)90355-7
  5. Cecchinato, V., Chiaramonte, R., Nizzardo, M., Cristofaro, B., Basile, A., Sherbet, G. V. and Comi, P. (2007). Resveratrolinduced apoptosis in human T-cell acute lymphoblastic leukaemia MOLT-4 cells. Biochem. Pharmacol. 74, 1568-1574 https://doi.org/10.1016/j.bcp.2007.08.001
  6. Chang, T. K., Lee, W. B. and Ko, H. H. (2000). Trans-resveratrol modulates the catalytic activity and mRNA expression of the procarcinogen-activating human cytochrome P450 1B1. Can. J. Physiol. Pharmacol. 78, 874-881 https://doi.org/10.1139/cjpp-78-11-874
  7. Chun, Y. J., Kim, M. Y. and Guengerich, F. P. (1999). Resveratrol is a selective human cytochrome P450 1A1 inhibitor. Biochem. Biophys. Res. Commun. 262, 20-24 https://doi.org/10.1006/bbrc.1999.1152
  8. Chun, Y. J. and Kim, S. (2003). Discovery of cytochrome P450 1B1 inhibitors as new anti-cancer agents. Med. Res. Rev. 23, 657-668 https://doi.org/10.1002/med.10050
  9. Chun, Y. J., Kim, S., Kim, D., Lee, S. K. and Guengerich, F. P. (2001a). A new selective and potent inhibitor of human cytochrome P450 1B1 and its application to antimutagenesis. Cancer Res. 61, 8164-8170
  10. Chun, Y. J., Lee, S.K. and Kim, M. Y. (2005). Modulation of human cytochrome P450 1B1 expression by 2,4,3',5'-tetramethoxystilbene. Drug Metab. Dispos. 33, 1771-1776 https://doi.org/10.1124/dmd.105.006502
  11. Chun, Y. J., Ryu, S. Y., Jeong, T. C. and Kim, M. Y. (2001b). Mechanism based inhibition of human cytochrome P450 1A1 by rhapontigenin. Drug Metab. Dispos. 29, 389-393
  12. Ferrigni, N. R., McLaughlin, J. L., Powell, R. G. and Smith, C. R. (1984). Isolation of piceatannol as the antileukemic principle from the seeds of euphorbia lagascae. J. Nat. Prod. 47, 347-352 https://doi.org/10.1021/np50032a019
  13. Fleming, I., Fisslthaler, B. and Busse, R. (1995). Calcium signaling in endothelial cells involves activation of tyrosine kinases and leads to activation of MAP kinases. Circ. Res. 76, 522-529 https://doi.org/10.1161/01.RES.76.4.522
  14. Gardai, S. J., Hildeman, D. A., Frankel, S. K., Whitlock, B. B., Frasch, S. C., Borregaard, N., Marrack, P., Bratton, D. L. and Henson, P. M. (2004). Phosphorylation of Bax Ser184 by Akt regulates its activity and apoptosis in neutrophils. J. Biol. Chem. 279, 21085-21095 https://doi.org/10.1074/jbc.M400063200
  15. Geahlen, R. L. and McLaughlin, J. L. (1989). Piceatannol (3,4,3',5'-tetrahydroxy-trans-stilbene) is a naturally occurring protein-tyrosine kinase inhibitor. Biochem. Biophys. Res. Commun. 165, 241-245 https://doi.org/10.1016/0006-291X(89)91060-7
  16. Gross, A., McDonnell, J. M. and Korsmeyer, S. J. (1999). Bcl-2 family members and the mitochondria in apoptosis. Genes Dev. 13, 1899-1911 https://doi.org/10.1101/gad.13.15.1899
  17. Guengerich, F. P., Martin, M. V., Guo, Z. and Chun, Y. J. (1996). Purification of functional recombinant P450s from bacteria. Methods Enzymol. 272, 35-44 https://doi.org/10.1016/S0076-6879(96)72006-2
  18. Guengerich, F. P. and Shimada, T. (1991). Oxidation of toxic and carcinogenic chemicals by human cytochrome P-450 enzymes. Chem. Res. Toxicol. 4,381-407 https://doi.org/10.1021/tx00022a001
  19. Hsieh, T., Juan, G., Darzynkiewicz, Z. and Wu, J. M. (1999). Resveratrol increases nitric oxide synthase, induces accumulation of p53 and p21(WAF1/CIP1), and suppresses cultured bovine pulmonary artery endothelial cell proliferation by perturbing progression through S and G2. Cancer Res. 59, 2596-2601
  20. Johnson, N. C., Dan, H. C., Cheng, J. Q. and Kruk, P. A. (2004). BRCA1 185delAG mutation inhibits Akt-dependent, IAPmediated caspase 3 inactivation in human ovarian surface epithelial cells. Exp. Cell Res. 298, 9-16 https://doi.org/10.1016/j.yexcr.2004.04.003
  21. Kadlubar, F. F. and Hammons, G. J. (1987). The role of cytochrome P-450 in the metabolism of chemical carcinogens. In: Mammalian cytochromes P-450. Boca Raton: CRC Press; 1987. pp 81-130
  22. Kennedy, S. G., Wagner, A. J., Conzen, S. D., Jordan, J., Bellacosa, A., Tsichlis, P. N. and Hay, N. (1997). The PI3-kinase/Akt signaling pathway delivers an anti-apoptotic signal. Genes Dev. 11, 701-713 https://doi.org/10.1101/gad.11.6.701
  23. Lee, S. K., Kim, Y., Kim, M. Y., Chun, Y. J. and Kim, S. (2004). Potent inhibition of recombinant human cytochrome P-450 1A1 by pentamethoxystilbene. J. Toxicol. Environ. Health Part A 67, 1987-2000 https://doi.org/10.1080/15287390490514642
  24. Lee, S. H., Ryu, S. Y., Kim, H. B., Kim, M. Y. and Chun, Y. J. (2002). Induction of apoptosis by 3,4'-dimethoxy-5-hydroxystilbene in human promyeloid leukemic HL-60 cells. Planta Med. 68, 123-127 https://doi.org/10.1055/s-2002-20242
  25. Li, Y., Liu, J. Y., Liu, X. P., Xing, K. F., Wang Y., Li, F. Y. and Yao, L. (2006). Resveratrol-induced cell inhibition of growth and apoptosis in MCF7 human breast cancer cells are associated with modulation of phosphorylated Akt and caspase-9. Appl. Biochem. Biotechnol. 135,181-192 https://doi.org/10.1385/ABAB:135:3:181
  26. Omura, T. and Sato, R. (1964). The carbon-monoxide binding pigment of liver microsomes. J. Biol. Chem. 239, 2370-2378
  27. Peters, J. D., Furlong, M. T., Asai, D. J., Harrison, M. L. and Geahlen, R. L. (1996). Syk, activated by cross-linking the Bcell antigen receptor, localises to the cytosol where it interacts with and phosphorylates a-tubulin on tyrosine. J. Biol. Chem. 271, 4755-4762 https://doi.org/10.1074/jbc.271.9.4755
  28. Parikh, A., Gillam, E. M. and Guengerich, F. P. (1997). Drug metabolism by Escherichia coli expressing human cytochromes P450. Nat. Biotechnol. 15, 784-788 https://doi.org/10.1038/nbt0897-784
  29. So, K. S., Oh, J. E., Han, J. H., Jung, H. K., Lee, Y. S., Kim, S. H., Chun, Y. J. and Kim, M. Y. (2008). Induction of apoptosis by a stilbene analog involves Bax translocation regulated by p38 MAPK and Akt. Arch. Pharm. Res. 31, 438-444 https://doi.org/10.1007/s12272-001-1176-7
  30. Su., L. and David, M. (2000). Distinct mechanisms of STAT phosphorylation via the interferon-a/b receptor, selective inhibition of STAT3 and STAT5 by piceatannol. J. Biol. Chem. 275, 12661-12666 https://doi.org/10.1074/jbc.275.17.12661
  31. Surh, Y. J., Hurh, Y. J., Kang, J. Y., Lee, E., Kong, G. and Lee, S. J. (1999). Resveratrol, an antioxidant present in red wine, induces apoptosis in human promyelocytic leukemia (HL-60) cells. Cancer Lett. 140, 1-10 https://doi.org/10.1016/S0304-3835(99)00039-7
  32. Tsan, M. F., White, J. E., Maheshwari, J. G., Bremner, T. A. and Sacco, J. (2000). Resveratrol induces Fas signalling-independent apoptosis in THP-1 human monocytic leukemia cells. Brit. J. Haematol. 109, 405-412 https://doi.org/10.1046/j.1365-2141.2000.01980.x
  33. Tsuruta, F., Masuyama, N. and Gotoh Y. (2002). The phosphatidylinositol 3-kinase (PI3K)-Akt pathway suppresses Bax translocation to mitochondria. J. Biol. Chem. 277, 14040-14047 https://doi.org/10.1074/jbc.M108975200
  34. Wrighton, S. A. and Stevens, J. C. (1992). The human hepatic cytochrome P450 involved in drug metabolism. Crit. Rev. Toxicol. 22,1-21 https://doi.org/10.3109/10408449209145319
  35. Zha, J., Harada, H., Yang, E., Jockel, J. and Korsmeyer, S. J. (1996). Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14-3-3- not Bcl-XL. Cell 87, 619-628 https://doi.org/10.1016/S0092-8674(00)81382-3
  36. Zhou, H., Li, X. M., Meinkoth, J. and Pittman, R. N. (2000). Akt regulates cell survival and apoptosis at a postmitochondrial level. J. Cell. Biol. 151, 483-494 https://doi.org/10.1083/jcb.151.3.483

Cited by

  1. Self-Sufficient Catalytic System of Human Cytochrome P450 4A11 and NADPH-P450 Reductase vol.17, pp.2, 2009, https://doi.org/10.4062/biomolther.2009.17.2.156
  2. Regioselective Oxidation of Lauric Acid by CYP119, an Orphan Cytochrome P450 from Sulfolobus acidocaldarius vol.20, pp.3, 2008, https://doi.org/10.4014/jmb.0909.09007
  3. Mechanism-based inactivation of cytochrome P450 enzymes by natural products based on metabolic activation vol.52, pp.4, 2008, https://doi.org/10.1080/03602532.2020.1828910