Molecular Biology Reports

, Volume 30, Issue 1, pp 41–46 | Cite as

Involvement of YY1 and its correlation with c-myc in NDEA induced hepatocarcinogenesis, its prevention by d-limonene

  • Tithi Parija
  • Bibhu Ranjan Das


Anticarcinogenic activity of d-limonene has been well documented within last few years. We have also reported the anticarcinogenic activity of d-limonene in N-nitrosodiethylamine (NDEA) induced hepatocarcinogenesis. The involvement of oncogenes which adds to the mechanisms of d-limonene mediated chemprevention were also suggested in the same model system. The overexpression of c-myc oncoprotein in different durations of NDEA induced hepatrocarcinogenesis is observed which is inhibited completely when d-limonene was treated prior to and along with NDEA. To work further in this direction, an attempt has been made here to know the role of YY1 (Yin Yang 1) transcription factor in N-nitrodiethylamine (NDEA) induced hepatocarcinogenesis and its chemoprevention by d-limonene. Electrophoretic mobility shift assay results have clearly indicated the binding of YY1 in control liver tissue. But this binding is blocked in 60 days and 150 days NDEA treated liver tumors. Thus, it is assumed that there is deregulation of YY1 transcription factor in NDEA induced hepatocarcinogenesis. A similar type of binding to that of control liver tissue has also observed when limonene was given prior to NDEA administration. Western blot analysis has shown inhibition of YY1 protein in NDEA induced liver tumor samples in comparison to normal and both NDEA and limonene treated samples. On the otherhand RT-PCR analysis does not indicate any correlation between YY1 mRNA level and inhibition of YY1 protein. However, along with our earlier information about c-myc with the present study, clearly indicated the involvement of YY1 in NDEA induced hepatocarcinogenesis and d-limonene mediated chemoprevention which might be regulated by c-myc oncoprotein.

c-myc d-limonene hepatrocarcinogenesis N-nitrosodithylamine (NDEA) YY1 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Gould MN, Moore CJ, Zhang R, Wang B, Kennam WS & Haag JD (1994) Canc. Res. 54: 3540–3543.Google Scholar
  2. 2.
    Giri RK, Parija T & Das BR (1999) Oncol. Rep. 6: 1123-1127.Google Scholar
  3. 3.
    Uedo N, Tatsuta M, Iishi H, Baba M, Sakai N, Yano H & Otani T (1999) Canc. Lett. 137: 131–136.Google Scholar
  4. 4.
    Kaji I, Tatsatu M, Iishi H, Baba M, Inoue A & Kasugei H, (2001) Int. J. Cancer 93: 441–444.Google Scholar
  5. 5.
    Mc Namee D (1993) Lancet 342: 801.Google Scholar
  6. 6.
    Srivastava A, Yu J, Artandi S & Calame K (1996) Proc. Natl. Acad. Sci. USA 93: 10638–10641Google Scholar
  7. 7.
    Galvin KM & Shi Y (1997) Mol. Cell Biol. 17: 3723-3732.Google Scholar
  8. 8.
    Shrivastava A & Calame K (1994) Nuc. Acid Res. 22: 5151–5155.Google Scholar
  9. 9.
    Lee TC, Zhang Y & Schwartz RJ (1994) Oncogene 9: 1047–1052.Google Scholar
  10. 10.
    Lee TC, Shi Y & Schwartz RJ (1992) PNAS, USA 89: 9814–9818.Google Scholar
  11. 11.
    Rought B, Khursheed B, Kazanchy A & Rosen J (1994) MCB 14: 1752–1763.Google Scholar
  12. 12.
    Bauknecht T, Angel P, Royer HD & Zur Hausen H (1992) EMBO J. 11: 4607–4617.Google Scholar
  13. 13.
    May M, Dong XP, Bayer-Finkler E., Stubenrauch F, Fuchs PG & Pfister H, EMBO. J. 13: 1460–1466.Google Scholar
  14. 14.
    Shi Y, Seto E, Chang LS & Shenk T (1991) Cell 67: 377–388.Google Scholar
  15. 15.
    Hariharan N, Kelley D & Perry RP (1991) PNAS, USA 88: 9799–9803.Google Scholar
  16. 16.
    Riggs KJ, Saleque S, Wong KK, Merrell KT, Lee JS, Shi Y & Calame K (1993) Mol. Cell Biol. 13: 7487–7495.Google Scholar
  17. 17.
    Austen M, Cerni C, Luscher-Firzlaff JM & Luscher B (1998) Oncogene 17: 511–520.Google Scholar
  18. 18.
    Srivastava A, Saleque S, Kalpana GV, Artandi S, Goff SP & Calame K (1993) Science 262: 1889–1892.Google Scholar
  19. 19.
    Parka V-G, Songc C-W, Morib N, Sugimotoa K, Honga D-P & Okumoto M (2000) Canc. Lett. 148: 95–103.Google Scholar
  20. 20.
    Scheiber E, Mutthias P & Schaffner W (1989) Nuc. Acid Res. 17: 6419.Google Scholar
  21. 21.
    Nayak BK, Patnaik S & Das BR (1998) Biochem. Biophys. Res. Comm. 245: 388-391.Google Scholar
  22. 22.
    Lichy JM, Majidi M, Elbaum J & Tsai MM (1996) Nuc. Acid Res. 24: 4700–4708.Google Scholar
  23. 23.
    Flanagan JR, Becker KG, Ennist DL, Gleason SL, Driggers PH, Levi BZ, Appella E & Ozato K (1992) Mol. Cell Biol. 12: 38–44.Google Scholar
  24. 24.
    Walowitz JL, Bradley ME, Chen S & Lee Techung, (1998) J. Biol. Chem. 273: 6656–6661.Google Scholar
  25. 25.
    Lee TC & Schwartz RJ (1992) Biotechniques 12: 486–490.Google Scholar
  26. 26.
    Dong XP, Stubenrauch F, Bayer-Finkler E & Pfister H (1994) Int. J. Cancer 58: 803–808.Google Scholar
  27. 27.
    Janssens V, Van Hoof C, De Balre I, Merlevede W & Goris J (2000) J. Biol. Chem. 275: 20488–20495.Google Scholar

Copyright information

© Kluwer Academic Publishers 2003

Authors and Affiliations

  • Tithi Parija
    • 1
  • Bibhu Ranjan Das
    • 1
  1. 1.Molecular Oncology and Medical Biotechnology DivisionInstitute of Life Sciences, Nalco Square, ChandrasekharpurBhubaneswar -India

Personalised recommendations