Regulation of Cox-2 by cyclic AMP response element binding protein in prostate cancer

Potential role for nexrutine

Rita Ghosh, Gretchen E. Garcia, Katherine Crosbyy, Hiroyasu Inouez, Ian M. Thompson, Dean A. Troyer, Addanki P Kumar

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

We recently showed that NexrutineR, a Phellodendron amurense bark extract, suppresses proliferation of prostate cancer cell lines and tumor development in the transgenic adenocarcinoma of mouse prostate (TRAMP) model. Our data also indicate that the antiproliferative effects of Nexrutine R are mediated in part by Akt and Cyclic AMP response element binding protein (CREB). Cyclooxygenase (Cox-2), a pro-inflammatory mediator, is a CREB target that induces prostaglandin E2 (PGE2) and suppresses apoptosis. Treatment of LNCaP cells with NexrutineR reduced tumor necrosis factor α-induced enzymatic as well as promoter activities of Cox-2. NexrutineR also reduced the expression and promoter activity of Cox-2 in PC-3 cells that express high constitutive levels of Cox-2. Deletion analysis coupled with mutational analysis of the Cox-2 promoter identified CRE as being sufficient for mediating NexrutineR response. Immunohistochemical analysis of human prostate tumors show increased expression of CREB and DNA binding activity in high-grade tumors (three-fold higher in human prostate tumors compared to normal prostate; P = .01). We have identified CREB-mediated activation of Cox-2 as a potential signaling pathway in prostate cancer which can be blocked with a nontoxic, cost-effective dietary supplement like NexrutineR, demonstrating a prospective for development of NexrutineR for prostate cancer management.

Original languageEnglish (US)
Pages (from-to)893-899
Number of pages7
JournalNeoplasia
Volume9
Issue number11
DOIs
StatePublished - Nov 2007

Fingerprint

Cyclic AMP Response Element-Binding Protein
Prostate
Prostatic Neoplasms
Phellodendron
Neoplasms
Cyclooxygenase 2
Dietary Supplements
Tumor Cell Line
Dinoprostone
Protein Binding
Transgenic Mice
Adenocarcinoma
Tumor Necrosis Factor-alpha
Apoptosis
Costs and Cost Analysis
Nexrutine
DNA

Keywords

  • Cox-2 promoter activity
  • CREB
  • Inflammation
  • PGE
  • Prostate cancer

ASJC Scopus subject areas

  • Cancer Research

Cite this

Regulation of Cox-2 by cyclic AMP response element binding protein in prostate cancer : Potential role for nexrutine. / Ghosh, Rita; Garcia, Gretchen E.; Crosbyy, Katherine; Inouez, Hiroyasu; Thompson, Ian M.; Troyer, Dean A.; Kumar, Addanki P.

In: Neoplasia, Vol. 9, No. 11, 11.2007, p. 893-899.

Research output: Contribution to journalArticle

Ghosh, Rita ; Garcia, Gretchen E. ; Crosbyy, Katherine ; Inouez, Hiroyasu ; Thompson, Ian M. ; Troyer, Dean A. ; Kumar, Addanki P. / Regulation of Cox-2 by cyclic AMP response element binding protein in prostate cancer : Potential role for nexrutine. In: Neoplasia. 2007 ; Vol. 9, No. 11. pp. 893-899.
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