Suppression of NFkappaB and its regulated gene products by oral administration of green tea polyphenols in an autochthonous mouse prostate cancer model

Pharm Res. 2008 Sep;25(9):2135-42. doi: 10.1007/s11095-008-9553-z. Epub 2008 Mar 4.

Abstract

Purpose: This study examines the role of cell survival/apoptosis related proteins involved in NFkappaB 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 NFkappaB and its regulated pathway in response to GTP.

Results: Our data demonstrated increased expression of NFkappaB, IKKalpha, IKKbeta, 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 NFkappaB 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 NFkappaB signaling that may contribute to induction of apoptosis observed in GTP fed TRAMP mice.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Adenocarcinoma / prevention & control
  • Administration, Oral
  • Animals
  • Anticarcinogenic Agents / administration & dosage*
  • Anticarcinogenic Agents / isolation & purification
  • Apoptosis / drug effects
  • Camellia sinensis* / chemistry
  • Down-Regulation
  • Flavonoids / administration & dosage*
  • Flavonoids / isolation & purification
  • Gene Expression Regulation, Neoplastic / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • NF-kappa B / metabolism*
  • Osteopontin / metabolism
  • Phenols / administration & dosage*
  • Phenols / isolation & purification
  • Polyphenols
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / prevention & control
  • Protein-Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Receptor Activator of Nuclear Factor-kappa B / metabolism
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction / drug effects*
  • Time Factors
  • bcl-2-Associated X Protein

Substances

  • Anticarcinogenic Agents
  • Bax protein, mouse
  • Flavonoids
  • NF-kappa B
  • Phenols
  • Polyphenols
  • Proto-Oncogene Proteins c-bcl-2
  • Receptor Activator of Nuclear Factor-kappa B
  • STAT3 Transcription Factor
  • Spp1 protein, mouse
  • Stat3 protein, mouse
  • Tnfrsf11a protein, mouse
  • bcl-2-Associated X Protein
  • Osteopontin
  • Protein-Serine-Threonine Kinases
  • NF-kappa B kinase