Skip to main content

Advertisement

SpringerLink
Log in

Suppression of NFκB and its Regulated Gene Products by Oral Administration of Green Tea Polyphenols in an Autochthonous Mouse Prostate Cancer Model

  • Research Paper
  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

Purpose

This study examines the role of cell survival/apoptosis related proteins involved in NFκB signaling pathways and its associated events in GTP-induced chemoprevention of prostate cancer in TRAMP mice.

Methods

Mice were given 0.1% GTP as drinking fluid. Western blot and immunohistochemical analysis performed to examine NFκB and its regulated pathway in response to GTP.

Results

Our data demonstrated increased expression of NFκB, IKKα, IKKβ, RANK, NIK and STAT-3 in dorso-lateral prostate of TRAMP mice as a function of age and tumor growth and continuous GTP infusion for 32 weeks resulted in substantial reduction in these proteins. The levels of transcription factor osteopontin, a non-collagenous extracellular matrix protein, were also downregulated. Inhibition of NFκB signaling is known to activate apoptotic and inhibit anti-apoptotic proteins. Therefore, we analyzed Bax and Bcl2 levels in the dorsolateral prostate of TRAMP mice fed GTP and observed a shift in balance between Bax and Bcl2 favoring apoptosis.

Conclusions

Based on the data we suggest that oral consumption of GTP might inhibit osteopontin and NFκB signaling that may contribute to induction of apoptosis observed in GTP fed TRAMP mice.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. J. D. Albano, E. Ward, A. Jemal, R. Anderson, V. E. Cokkinides, T. Murray, J. Henley, J. Liff, and M. J. Thun. Cancer mortality in the United States by education level and race. J. Natl. Cancer Inst. 99:1384–1394 (2007).

    Article  PubMed  Google Scholar 

  2. A. Jemal, R. Siegel, E. Ward, T. Murray, J. Xu, and M. J. Thun. Cancer statistics, 2007. CA. Cancer J. Clin. 57:43–66 (2007).

    Article  PubMed  Google Scholar 

  3. A. W. Hsing, L. Tsao, and S. S. Devesa. International trends and patterns of prostate cancer incidence and mortality. Int. J. Cancer 85:60–67 (2000).

    Article  PubMed  CAS  Google Scholar 

  4. M. Quinn and P. Babb. Patterns and trends in prostate cancer incidence, survival, prevalence and mortality. Part I: international comparisons. BJU Int. 90:162–173 (2002).

    Article  PubMed  CAS  Google Scholar 

  5. H. G. Sim and C. W. Cheng. Changing demography of prostate cancer in Asia. Eur. J. Cancer 41:834–845 (2005).

    Article  PubMed  Google Scholar 

  6. D. N. Syed, N. Khan, F. Afaq, and H. Mukhtar. Chemoprevention of prostate cancer through dietary agents: progress and promise. Cancer Epidemiol. Biomarkers Prev. 16:2193–2203 (2007).

    Article  PubMed  CAS  Google Scholar 

  7. I. A. Siddiqui, M. Saleem, V. M. Adhami, M. Asim, and H. Mukhtar. Tea beverage in chemoprevention and chemotherapy of prostate cancer. Acta. Pharmacol. Sin. 28:1392–1408 (2007).

    Article  PubMed  CAS  Google Scholar 

  8. E. D. Canby-Hagino and I. M. Thompson. Mechanisms of disease: prostate cancer—a model for cancer chemoprevention in clinical practice. Nat. Clin. Pract. Oncol. 2:255–261 (2005).

    Article  PubMed  Google Scholar 

  9. I. A. Siddiqui, F. Afaq, V. M. Adhami, and H. Mukhtar. Prevention of prostate cancer through custom tailoring of chemopreventive regimen. Chem. Biol. Interact. 171:122–132 (2008).

    Article  PubMed  CAS  Google Scholar 

  10. S. Bettuzzi, M. Brausi, F. Rizzi, G. Castagnetti, G. Peracchia, and A. Corti. Chemoprevention of human prostate cancer by oral administration of green tea catechins in volunteers with high-grade prostate intraepithelial neoplasia: a preliminary report from a one-year proof-of-principle study. Cancer Res. 66:1234–1240 (2006).

    Article  PubMed  CAS  Google Scholar 

  11. M. G. Neill and N. E. Fleshner. An update on chemoprevention strategies in prostate cancer for 2006. Curr. Opin. Urol. 16:132–137 (2006).

    Article  PubMed  Google Scholar 

  12. V. M. Adhami, I. A. Siddiqui, N. Ahmad, S. Gupta, and H. Mukhtar. Oral consumption of green tea polyphenols inhibits insulin-like growth factor-I-induced signaling in an autochthonous mouse model of prostate cancer. Cancer Res. 64:8715–8722 (2004).

    Article  PubMed  CAS  Google Scholar 

  13. W. Liu, Y. Liu, and W. L. Lowe Jr. The role of phosphatidylinositol 3-kinase and the mitogen-activated protein kinases in insulin-like growth factor-I-mediated effects in vascular endothelial cells. Endocrinology 142:1710–1719 (2001).

    Article  PubMed  CAS  Google Scholar 

  14. F. Garrouste, M. Remacle-Bonnet, C. Fauriat, J. Marvaldi, J. Luis, and G. Pommier. Prevention of cytokine-induced apoptosis by insulin-like growth factor-I is independent of cell adhesion molecules in HT29-D4 colon carcinoma cells-evidence for a NF-kappaB-dependent survival mechanism. Cell Death Differ. 9:768–779 (2002).

    Article  PubMed  CAS  Google Scholar 

  15. N. M. Greenberg, F. DeMayo, M. J. Finegold, D. Medina, W. D. Tilley, J. O. Aspinall, G. R. Cunha, A. A. Donjacour, R. J. Matusik, and J. M. Rosen. Prostate cancer in a transgenic mouse. Proc. Natl. Acad. Sci. U S A 92:3439–3443 (1995).

    Article  PubMed  CAS  Google Scholar 

  16. S. Gupta, K. Hastak, N. Ahmad, J. S. Lewin, and H. Mukhtar. Inhibition of prostate carcinogenesis in TRAMP mice by oral infusion of green tea polyphenols. Proc. Natl. Acad. Sci. U S A 98:10350–10355 (2001).

    Article  PubMed  CAS  Google Scholar 

  17. I. A. Siddiqui, N. Zaman, M. H. Aziz, S. R. Reagan-Shaw, S. Sarfaraz, V. M. Adhami, N. Ahmad, S. Raisuddin, and H. Mukhtar. Inhibition of CWR22Rnu1 tumor growth and PSA secretion in athymic nude mice by green and black teas. Carcinogenesis. 27:833–839 (2006).

    Article  PubMed  CAS  Google Scholar 

  18. A. C. Bharti, Y. Takada, S. Shishodia, and B. B. Aggarwal. Evidence that receptor activator of nuclear factor (NF)-kappaB ligand can suppress cell proliferation and induce apoptosis through activation of a NF-kappaB-independent and TRAF6-dependent mechanism. J. Biol. Chem. 279:6065–6076 (2004).

    Article  PubMed  CAS  Google Scholar 

  19. S. S. Forootan, C. S. Foster, V. R. Aachi, J. Adamson, P. H. Smith, K. Lin, and Y. Ke. Prognostic significance of osteopontin expression in human prostate cancer. Int. J. Cancer 118:2255–2261 (2006).

    Article  PubMed  CAS  Google Scholar 

  20. B. E. Barton, J. G. Karras, T. F. Murphy, A. Barton, and H. F. Huang. Signal transducer and activator of transcription 3 (STAT3) activation in prostate cancer: direct STAT3 inhibition induces apoptosis in prostate cancer lines. Mol. Cancer Ther. 3:11–20 (2004).

    PubMed  CAS  Google Scholar 

  21. M. H. Aziz, H. T. Manoharan, D. R. Church, N. E. Dreckschmidt, W. Zhong, T. D. Oberley, G. Wilding, and A. K. Verma. Protein kinase Cepsilon interacts with signal transducers and activators of transcription 3 (Stat3), phosphorylates Stat3Ser727, and regulates its constitutive activation in prostate cancer. Cancer Res. 67:8828–8838 (2007).

    Article  PubMed  CAS  Google Scholar 

  22. S. Shukla, G. T. Maclennan, S. R. Marengo, M. I. Resnick, and S. Gupta. Constitutive activation of P I3 K-Akt and NF-kappaB during prostate cancer progression in autochthonous transgenic mouse model. Prostate. 64:224–239 (2005).

    Article  PubMed  CAS  Google Scholar 

  23. J. Suh, F. Payvandi, L. C. Edelstein, P. S. Amenta, W. X. Zong, C. Gélinas, and A. B. Rabson. Mechanisms of constitutive NF-kappaB activation in human prostate cancer cells. Prostate. 52:183–200 (2002).

    Article  PubMed  CAS  Google Scholar 

  24. J. Suh and A. B. Rabson. NF-kappaB activation in human prostate cancer: important mediator or epiphenomenon? J. Cell Biochem. 91:100–117 (2004).

    Article  PubMed  CAS  Google Scholar 

  25. B. B. Hafeez, S. Ahmed, N. Wang, S. Gupta, A. Zhang, and T. M. Haqqi. Green tea polyphenols-induced apoptosis in human osteosarcoma SAOS-2 cells involves a caspase-dependent mechanism with downregulation of nuclear factor-kappaB. Toxicol. Appl. Pharmacol. 216:11–19 (2006).

    Article  PubMed  CAS  Google Scholar 

  26. J. Bromberg. Signal transducers and activators of transcription as regulators of growth, apoptosis and breast development. Breast Cancer Res. 2:86–90 (2000).

    Article  PubMed  CAS  Google Scholar 

  27. L. Pedranzini, A. Leitch, and J. Bromberg. Stat3 is required for the development of skin cancer. J. Clin. Invest. 114:619–622 (2004).

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This original work for author’s laboratory was supported by US PHS Grants RO1 CA 78809; RO1 CA 101039, RO1 CA 120451 and O’Brian center Grant P50 DK065303-01.

Author information

Authors and Affiliations

  1. Department of Dermatology, University of Wisconsin, Madison, Wisconsin, 53706, USA

    Imtiaz A. Siddiqui, Vaqar M. Adhami, Sami Sarfaraz, Mohammad Asim, Bilal Bin Hafeez & Hasan Mukhtar

  2. Proteomics Laboratory, Indian Institute of Toxicology Research, 80 MG Marg, Lucknow, 226001, India

    Yogeshwer Shukla

  3. Department of Dermatology, Medical Sciences Center, University of Wisconsin, B-25, 1300 University Avenue, Madison, Wisconsin, 53706, USA

    Hasan Mukhtar

Authors
  1. Imtiaz A. Siddiqui
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yogeshwer Shukla
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vaqar M. Adhami
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sami Sarfaraz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mohammad Asim
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Bilal Bin Hafeez
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hasan Mukhtar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hasan Mukhtar.

Additional information

Imtiaz A. Siddiqui and Yogeshwer Shukla contributed equally to this manuscript.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Siddiqui, I.A., Shukla, Y., Adhami, V.M. et al. Suppression of NFκB and its Regulated Gene Products by Oral Administration of Green Tea Polyphenols in an Autochthonous Mouse Prostate Cancer Model. Pharm Res 25, 2135–2142 (2008). https://doi.org/10.1007/s11095-008-9553-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11095-008-9553-z

Key words

Search

Navigation