Regulation of Cox-2 by Cyclic AMP Response Element Binding Protein in Prostate Cancer: Potential Role for Nexrutine
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 NexrutineR are mediat...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2007-11-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558607800170 |
| _version_ | 1828553022753472512 |
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| author | Rita Ghosh Gretchen E. Garcia Katherine Crosby Hiroyasu Inoue Ian M. Thompson Dean A. Troyer Addanki P. Kumar |
| author_facet | Rita Ghosh Gretchen E. Garcia Katherine Crosby Hiroyasu Inoue Ian M. Thompson Dean A. Troyer Addanki P. Kumar |
| author_sort | Rita Ghosh |
| collection | DOAJ |
| description | 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 NexrutineR 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. |
| first_indexed | 2024-12-12T05:11:35Z |
| format | Article |
| id | doaj.art-3351bdc01e3f4eea8c21a21671ae8878 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-12-12T05:11:35Z |
| publishDate | 2007-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-3351bdc01e3f4eea8c21a21671ae88782022-12-22T00:36:53ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022007-11-0191189389910.1593/neo.07502Regulation of Cox-2 by Cyclic AMP Response Element Binding Protein in Prostate Cancer: Potential Role for NexrutineRita Ghosh0Gretchen E. Garcia1Katherine Crosby2Hiroyasu Inoue3Ian M. Thompson4Dean A. Troyer5Addanki P. Kumar6The Sandra and Stanley Rosenberg Family Laboratories, Department of Urology, University of Texas Health Science Center, San Antonio, TX 78229, USAThe Sandra and Stanley Rosenberg Family Laboratories, Department of Urology, University of Texas Health Science Center, San Antonio, TX 78229, USACell Signaling Technology, Inc., Danvers, MA, USADepartment of Food Science and Nutrition, Faculty of Human Life and Environment, Nara Women's University, Kita-Uoya-Nishimachi, Nara 630-8506, JapanThe Sandra and Stanley Rosenberg Family Laboratories, Department of Urology, University of Texas Health Science Center, San Antonio, TX 78229, USADepartment of Pathology, University of Texas Health Science Center, San Antonio, TX 78229, USAThe Sandra and Stanley Rosenberg Family Laboratories, Department of Urology, University of Texas Health Science Center, San Antonio, TX 78229, USAWe 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 NexrutineR 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.http://www.sciencedirect.com/science/article/pii/S1476558607800170Cox-2 promoter activityprostate cancerCREBinflammationPGE2 |
| spellingShingle | Rita Ghosh Gretchen E. Garcia Katherine Crosby Hiroyasu Inoue Ian M. Thompson Dean A. Troyer Addanki P. Kumar Regulation of Cox-2 by Cyclic AMP Response Element Binding Protein in Prostate Cancer: Potential Role for Nexrutine Neoplasia: An International Journal for Oncology Research Cox-2 promoter activity prostate cancer CREB inflammation PGE2 |
| title | Regulation of Cox-2 by Cyclic AMP Response Element Binding Protein in Prostate Cancer: Potential Role for Nexrutine |
| title_full | Regulation of Cox-2 by Cyclic AMP Response Element Binding Protein in Prostate Cancer: Potential Role for Nexrutine |
| title_fullStr | Regulation of Cox-2 by Cyclic AMP Response Element Binding Protein in Prostate Cancer: Potential Role for Nexrutine |
| title_full_unstemmed | Regulation of Cox-2 by Cyclic AMP Response Element Binding Protein in Prostate Cancer: Potential Role for Nexrutine |
| title_short | Regulation of Cox-2 by Cyclic AMP Response Element Binding Protein in Prostate Cancer: Potential Role for Nexrutine |
| title_sort | regulation of cox 2 by cyclic amp response element binding protein in prostate cancer potential role for nexrutine |
| topic | Cox-2 promoter activity prostate cancer CREB inflammation PGE2 |
| url | http://www.sciencedirect.com/science/article/pii/S1476558607800170 |
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