>> Главная

Role of p53 and NF-kappaB in epigallocatechin-3-gallate-induced apoptosis of LNCaP cells.

Oncogene 2003 Jul 31;22(31):4851-9           

Hastak K; Gupta S ; Ahmad N; Agarwal MK; Agarwal ML; Mukhtar H
Department of Environmental Health Sciences, Case Western Reserve University, Cleveland, OH 44106, USA.

We have recently shown that oral consumption of green tea polyphenols inhibits prostate carcinogenesis in transgenic mouse model of prostate cancer and suggested that induction of apoptosis in prostate cancer cells is responsible for these effects. Much of the chemopreventive effects of green tea are attributed to its major polyphenolic constituent (-) epigallocatechin-3-gallate (EGCG). In the present study, we report that EGCG-induced apoptosis in human prostate carcinoma LNCaP cells is mediated via modulation of two related pathways: (a) stabilization of p53 by phosphorylation on critical serine residues and p14ARF-mediated downregulation of murine double minute 2(MDM2) protein, and (b) negative regulation of NF-kappaB activity, thereby decreasing the expression of the proapoptotic protein Bcl-2. EGCG-induced stabilization of p53 caused an upregulation in its transcriptional activity, thereby resulting in activation of its downstream targets p21/WAF1 and Bax. Thus, EGCG had a concurrent effect on two important transcription factors p53 and NF-kappaB, causing a change in the ratio of Bax/Bcl-2 in a manner that favors apoptosis. This altered expression of Bcl-2 family members triggered the activation of initiator capsases 9 and 8 followed by activation of effector caspase 3. Activation of the caspases was followed by poly (ADP-ribose) polymerase cleavage and induction of apoptosis. Taken together, the data indicate that EGCG induces apoptosis in human prostate carcinoma cells by shifting the balance between pro- and antiapoptotic proteins in favor of apoptosis.



Type a keyword and click on the 'Go' button to begin full-text search throughout the site.

 Printer-friendly page

Send page to a friend Send page to a friend

Bookmark this page Bookmark this page

>> Natural Health Care

>> Studies Worldwide

>> "Business With Disease"

>> International Campaign

>> Open Letter Campaign

>> Take Action

>> Features

 © 2019 Dr. Rath Health Foundation Send page to a friend contact Printer-friendly page Help Previous document Top of the page Function not available in this page Back to Homepage