Korean Journal of Pharmacognosy (생약학회지)

The Korean Society of Pharmacognosy (한국생약학회)
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Effect of the Hesperetin and Naringenin on $pp60^{v-src}$-induced $NF-{\kappa}B$ Activation

$pp60^{v-src}$에 의한 $NF-{\kappa}B$ 활성화에 대한 헤스페레틴과 나린제닌의 저해 효과

  • Kwon, O-Song (Laboratory of Cellular Signaling Modulators, Korea Research Institute of Bioscience and Biotechnology) ;
  • Kim, Bo-Yeon (Laboratory of Cellular Signaling Modulators, Korea Research Institute of Bioscience and Biotechnology) ;
  • Kim, Kyoung-A (Laboratory of Cellular Signaling Modulators, Korea Research Institute of Bioscience and Biotechnology) ;
  • Kim, Min-Soo (Laboratory of Cellular Signaling Modulators, Korea Research Institute of Bioscience and Biotechnology) ;
  • Oh, Hyun-Cheol (Laboratory of Cellular Signaling Modulators, Korea Research Institute of Bioscience and Biotechnology) ;
  • Kim, Beom-Seok (Laboratory of Cellular Signaling Modulators, Korea Research Institute of Bioscience and Biotechnology) ;
  • Kim, Young-Ho (Department of Manufacturing Pharmacy, Chungnam National University) ;
  • Ahn, Jong-Seog (Laboratory of Cellular Signaling Modulators, Korea Research Institute of Bioscience and Biotechnology)
  • 권오송 (한국생명공학연구원 세포신호조절연구실) ;
  • 김보연 (한국생명공학연구원 세포신호조절연구실) ;
  • 김경아 (한국생명공학연구원 세포신호조절연구실) ;
  • 김민수 (한국생명공학연구원 세포신호조절연구실) ;
  • 오현철 (한국생명공학연구원 세포신호조절연구실) ;
  • 김범석 (한국생명공학연구원 세포신호조절연구실) ;
  • 김영호 (충남대학교 제약학과) ;
  • 안종석 (한국생명공학연구원 세포신호조절연구실)
  • Published : 2004.09.30
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Abstract

The effects of hesperetin and naringenin on $NF-{\kappa}B$ activation were investigated in normal rat kidney cells transformed by temperature sensitive Rous Sarcoma Virus (tsNRK). The flavonoids, naringenin and hesperetin, significantly reduced v-Src-induced $NF-{\kappa}B$ activation as well as phosphorylation of Akt and GSK-3 in tsNRK cells, whereas these compounds did not effect on platelet-derived growth factor (PDGF)-induced $NF-{\kappa}B$ activation in $NIH3T3{\gamma}l$ cells. In addition, the DNA binding activity of SP-I was also reduced but that of AP-1 was not affected by the compounds. Our study suggests that Src-induced $NF-{\kappa}B$ activation could occur via Akt-GSK-3 pathway without $IkB{\alpha}$ degradation and that naringenin and hesperetin could be used in the treatment of cancer through the inhibition of $NF-{\kappa}B$ activation.

Keywords

References

  1. Kuo, S. M. (1996) Antiproliferative potency of structurally distinct dietary flavonoids human colon cancer cells. Cancer. Lett. 110: 41-48 https://doi.org/10.1016/S0304-3835(96)04458-8
  2. Robak, J. and Gryflewski, R. J. (1998) Flavonoids are scavengers of sliperoxide anions. Biachem. Pharmacal. 37: 837-84l
  3. Miksicek, R. J. (1993) Commonly occurring plant flavonoids have estrogenic activity. Mal. Pharmacal. 44: 37-43
  4. Le Bail, J. C., Vamat, F., Nicolas, J. C. and Habrioux, G. (1998) Estrogenic and antiproliferative activities on MCF-7 human breast cancer cells by flavonoids. Cancer. Lett. 130: 209-216 https://doi.org/10.1016/S0304-3835(98)00141-4
  5. Akiyama, T., Ishida, J., Nakagawa, S., Ogawara, H., Watanabe, S., Itoh, N., Shibuya, M. and Fukami, Y. (1987) Genistein, a specific inhibitor of tyrosine-specific protein kinases. J. Bial. Chem. : 5592-5595
  6. Hagiwara, M., Inoue, S., Tanaka, T., Nunoki, K., Ito, M. and Hidaka, H. (1998) Differential effects offlavonoids inhibitors of tyrosine protein kinases and serine/threonine protein kinases. Biachem. Pharmacal. 37: 2987-2992
  7. Yamashita, Y., Kawada, S. and Nakano, H. (1990) Induction of mammalian topoisomerasell dependent DNA cleavage by nonintercalative flavonoids, genistein and orobol. Biochem. Phannacol. 39: 737-744 https://doi.org/10.1016/0006-2952(90)90153-C
  8. Ruh, M. F, Zacharewski, T., Connor, K., Howell, J., Chen, I. and Safe, S. (1995) Naringenin: A weakly estrogenic bioflavonoid that exhibits antiestrogenic activity. Biochem. Phannacol. 50: 1485-1493 https://doi.org/10.1016/0006-2952(95)02061-6
  9. Van Acker, F. A., Schouten, O., Haenen, G. R, van der Vijgh, W. J. and Bast, A. (2000) Flavonoids can replace atocopherol as an antioxidant. FEBS. Lett. 473: 145-148 https://doi.org/10.1016/S0014-5793(00)01517-9
  10. Santos, K F., Oliveira, T. T., Nagem, T. J., Pinto, A. S. and Oliveira, M. G. (1999) Hypolipidaemkic effects of naringenin, rutin, nicotinic acid and their associations. Pharmacol. Res. 40: 493-496 https://doi.org/10.1006/phrs.1999.0556
  11. Paredes, A, Alzuru, M., Mendez, J. and Rodriguez-Ortega, M. (2003) Anti-Sindbis activity of flavanones hesperetin and naringenin. BioI. Pharm. Bull. 26: 108-109 https://doi.org/10.1248/bpb.26.108
  12. Harmon, A. W. and Patel, Y. M. (2003) Naringenin inhibits phosphoinositide 3-kinase activity and glucose uptake in 3T3-Ll adipocytes. Biochem. Biophys. Res. Commun. 305: 229-234 https://doi.org/10.1016/S0006-291X(03)00720-4
  13. Schwabe, R. F. and Brenner, D. A. (2002) Role of glycogen synthase kinase-3 in TNF-a-induced NF-KE activation and apoptosis in hepatocytes. Am. J. Physiol. Gastrointest. Liver Physiol. 283: G204-G211 https://doi.org/10.1152/ajpgi.00016.2002
  14. Hoeflich, K. P., Luo, J., Rubie, E. A., Tsao, M. S., Jin, O. and Woodgett, J. R. (2000) Requirement for glycogen synthase kinase$-\beta$ in cell survival and NF-KE activation. Nature 406: 86-90 https://doi.org/10.1038/35017574
  15. Neri, L. M., Borgatti, P., Capitani, S. and Marteli, A. M. (2002) The nuclear phosphoinositide 3-kinase/AKT pathway: a new second messenger system. Biochim. Biophys. Acta. 1584: 73-80 https://doi.org/10.1016/S1388-1981(02)00300-1
  16. Ghosh, S. and Karin, M. (2002) Missing pieces in the NF-KB puzzle. Cell 109 Suppl: S81-96 https://doi.org/10.1016/S0092-8674(02)00703-1
  17. Abu-Amer, Y, Ross, F. P., McHugh, K. P., Livolsi, A., Peyron, J. F. and Teitelbaum, S. L. (1998) Tumor necrosis $factor-\alpha$ activation of nuclear transcription phosphorylation of ${I}\kappa{E}\alpha$. J. BioI. Chem. 273: 29417-29423 https://doi.org/10.1074/jbc.273.45.29417
  18. Shain, K. H., Jove, Rand Olashaw, N. E. (1999) Constitutive RelB activation in v-Src-transformed fibroblasts : Requirement for $I\kappa{B}$ degradation. J. Cell. Biochem. 73: 237-247 https://doi.org/10.1002/(SICI)1097-4644(19990501)73:2<237::AID-JCB10>3.0.CO;2-H
  19. Huang, W. C., Chen, J. J. and Chen, C. C. (2003) c-Srcdependent tyrosine phosphorylation of $IKK\beta$ is involved in tumor necrosis factor-a induced intercellular adhesion molecule-l expression. J. BioI. Chem. 278: 9944-9952 https://doi.org/10.1074/jbc.M208521200
  20. Huang, W. C., Chen, J. J., Inoue, H. and Chen, C. C. (2003) Tyrosine phosphorylation of IKE $Kinase\alpha/\beta$ by protein kinase C-dependent c-Src activation is involved in TNF-ainduced cyclooxygenase-2 expression. J. Immunol. 170: 4767-4775 https://doi.org/10.4049/jimmunol.170.9.4767
  21. Storz, P. and Toker, A(2003) Protein kinase D mediates a stress-induced NF-kB activation and survival pathway. EMBO. J. 22: 109-120 https://doi.org/10.1093/emboj/cdg009
  22. Kim, B. Y, Kim, J. H., Han, Y. J., Ahn, S. C., Kang, D.O., Oh, W. K, Ko, H. R, Lee, H. S., Mheen, T. I. and Ahn, J. S.(l999) $pp60^{v-src}$ reactivation inhibits serum-induced accumulation of inositol phosphates and phosphatidylethanol in tsNRK. IUBMB Life. 48: 85-89 https://doi.org/10.1080/713803467
  23. Kim, B.Y Kang, D.O., Oh, W. K, Kim, J. H., Choi, Y. K., Jang, J. S., Suh, P. G., Ryu, S. H., Mheen, T. I., And Ahn, J. S. (2000) Involvement of SH2-SH2-SH3 domain of phospholipase Cyl in NF-KE signaling. FEBS. Lett. 472: 4549
  24. Romashkova, J. A and Makarov, S. S. (1999) ${NF}-\kappa{B}$ is a target of AKT in anti-apoptotic PDGF signalling. Nature 1: 86-90 https://doi.org/10.1038/001086a0