Suppression of NFkappaB and its regulated gene products by oral administration of green tea polyphenols in an autochthonous mouse prostate cancer model.
OBJECTIVE
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.
Siddiqui
Imtiaz A
IA
Department of Dermatology, University of Wisconsin, Madison, Wisconsin 53706, USA.
Shukla
Yogeshwer
Y
Adhami
Vaqar M
VM
Sarfaraz
Sami
S
Asim
Mohammad
M
Hafeez
Bilal Bin
BB
Mukhtar
Hasan
H
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D000284:Administration, Oral; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage* / Q000302:isolation & purification; D017209:Apoptosis / Q000187:drug effects; D028241:Camellia sinensis / Q000737:chemistry; D015536:Down-Regulation; D005419:Flavonoids / Q000008:administration & dosage* / Q000302:isolation & purification; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism*; D053495:Osteopontin / Q000378:metabolism; D010636:Phenols / Q000008:administration & dosage* / Q000302:isolation & purification; D059808:Polyphenols; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D051028:bcl-2-Associated X Protein; D000097782:NF-kappaB-Inducing Kinase
D016588:Anticarcinogenic Agents; D005419:Flavonoids; D016328:NF-kappa B; D053495:Osteopontin; D010636:Phenols; D059808:Polyphenols; D017346:Protein Serine-Threonine Kinases; D019253:Proto-Oncogene Proteins c-bcl-2; D053246:Receptor Activator of Nuclear Factor-kappa B; D050796:STAT3 Transcription Factor; D051028:bcl-2-Associated X Protein; D000097782:NF-kappaB-Inducing Kinase; C494827:Bax protein, mouse; C506896:Spp1 protein, mouse; C494087:Stat3 protein, mouse; C505687:Tnfrsf11a protein, mouse