Akt/cAMP-Responsive Element Binding Protein/Cyclin D1 Network: A Novel Target for Prostate Cancer Inhibition in Transgenic Adenocarcinoma of Mouse Prostate Model Mediated by Nexrutine, a Phellodendron Amurense Bark Extract
Purpose: Development of prostate cancer prevention strategies is an important priority to overcome high incidence, morbidity, and mortality. Recently, we showed that Nexrutine, an herbal extract, inhibits prostate cancer cell proliferation through modulation of Akt and cAMP-responsive element bindin...
Gespeichert in:
| Veröffentlicht in: | Clinical cancer research 2007-05, Vol.13 (9), p.2784-2794 |
|---|---|
| Hauptverfasser: | , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 2794 |
|---|---|
| container_issue | 9 |
| container_start_page | 2784 |
| container_title | Clinical cancer research |
| container_volume | 13 |
| creator | KUMAR, Addanki P BHASKARAN, Shylesh GANAPATHY, Manonmani CROSBY, Katherine DAVIS, Michael D KOCHUNOV, Peter SCHOOLFIELD, John YEH, I-Tien TROYER, Dean A GHOSH, Rita |
| description | Purpose: Development of prostate cancer prevention strategies is an important priority to overcome high incidence, morbidity, and
mortality. Recently, we showed that Nexrutine, an herbal extract, inhibits prostate cancer cell proliferation through modulation
of Akt and cAMP-responsive element binding protein (CREB)–mediated signaling pathways. However, it is unknown if Nexrutine
can be developed as a dietary supplement for the prevention of prostate cancer. In this study, we used the transgenic adenocarcinoma
of mouse prostate (TRAMP) model to examine the ability of Nexrutine to protect TRAMP mice from developing prostate cancer.
Experimental Design: Eight-week-old TRAMP mice were fed with pelleted diet containing 300 and 600 mg/kg Nexrutine for 20 weeks. Efficacy of Nexrutine
was evaluated by magnetic resonance imaging at 18 and 28 weeks of progression and histologic analysis of prostate tumor or
tissue at the termination of the experiment. Tumor tissue was analyzed for modulation of various signaling molecules.
Results: We show that Nexrutine significantly suppressed palpable tumors and progression of cancer in the TRAMP model. Expression
of total and phosphorylated Akt, CREB, and cyclin D1 was significantly reduced in prostate tissue from Nexrutine intervention
group compared with tumors from control animals. Nexrutine also inhibited cyclin D1 transcriptional activity in androgen-independent
PC-3 cells. Overexpression of kinase dead Akt mutant or phosphorylation-defective CREB inhibited cyclin D1 transcriptional
activity.
Conclusions: The current study shows that Nexrutine-mediated targeting of Akt/CREB–induced activation of cyclin D1 prevents the progression
of prostate cancer. Expression of CREB and phosphorylated CREB increased in human prostate tumors compared with normal tissue,
suggesting their potential use as prognostic markers. |
| doi_str_mv | 10.1158/1078-0432.CCR-06-2974 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_70460944</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>70460944</sourcerecordid><originalsourceid>FETCH-LOGICAL-c448t-b40a53914c652553d13b4bb5ca5ffa48844d1371718e9c5e2c09f94909f7d8f43</originalsourceid><addsrcrecordid>eNqFkt9u0zAUxiMEYmPwCCDfgLggq53YcbK7LBSYtI5qKteW45y0poldbHdbX5ZnwaVFveTG__T7vmP7O0nyluBLQlg5IZiXKaZ5dtk09yku0qzi9FlyThjjaZ4V7Hlc_2POklfe_8SYUILpy-SMcMrzjGTnye96HSaqns3Te_Aba7x-ADQdYAQT0LU2nTZLNHc2gDaTZqcGbdBngu4gPFq3vkI1urMPMKCFdEsIqLduT_sgA6BGGgUO3ZiVbnXQ1qAoXjhp_BKMVqjuwFglndLGjhLZHs3s1sPJYGa7aD2DTsddh9pdrPvktkEb-IQkmq9gGCJiOhe963HrwET5tXRrNH0KTqrwOnnRy8HDm-N8kfz4Ml0039Lb719vmvo2VZSWIW0pliyvCFUFyxjLO5K3tG2ZkqzvJS1LSuMRJ5yUUCkGmcJVX9Eqjrwre5pfJB8Ovhtnf23BBzFqr-L1pIH4JsExLXBF_w-SquQFw1UE2QFU8Te8g15snB6l2wmCxb4DxD5dsU9XxA4QuBD7Doi6d8cC23aE7qQ6Rh6B90dAeiWHPuahtD9xJa9odIrcxwO30svVo3Yg1N88HXiIma0EyUUlMl7S_A9_n8oD</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>19876509</pqid></control><display><type>article</type><title>Akt/cAMP-Responsive Element Binding Protein/Cyclin D1 Network: A Novel Target for Prostate Cancer Inhibition in Transgenic Adenocarcinoma of Mouse Prostate Model Mediated by Nexrutine, a Phellodendron Amurense Bark Extract</title><source>MEDLINE</source><source>American Association for Cancer Research</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>KUMAR, Addanki P ; BHASKARAN, Shylesh ; GANAPATHY, Manonmani ; CROSBY, Katherine ; DAVIS, Michael D ; KOCHUNOV, Peter ; SCHOOLFIELD, John ; YEH, I-Tien ; TROYER, Dean A ; GHOSH, Rita</creator><creatorcontrib>KUMAR, Addanki P ; BHASKARAN, Shylesh ; GANAPATHY, Manonmani ; CROSBY, Katherine ; DAVIS, Michael D ; KOCHUNOV, Peter ; SCHOOLFIELD, John ; YEH, I-Tien ; TROYER, Dean A ; GHOSH, Rita</creatorcontrib><description>Purpose: Development of prostate cancer prevention strategies is an important priority to overcome high incidence, morbidity, and
mortality. Recently, we showed that Nexrutine, an herbal extract, inhibits prostate cancer cell proliferation through modulation
of Akt and cAMP-responsive element binding protein (CREB)–mediated signaling pathways. However, it is unknown if Nexrutine
can be developed as a dietary supplement for the prevention of prostate cancer. In this study, we used the transgenic adenocarcinoma
of mouse prostate (TRAMP) model to examine the ability of Nexrutine to protect TRAMP mice from developing prostate cancer.
Experimental Design: Eight-week-old TRAMP mice were fed with pelleted diet containing 300 and 600 mg/kg Nexrutine for 20 weeks. Efficacy of Nexrutine
was evaluated by magnetic resonance imaging at 18 and 28 weeks of progression and histologic analysis of prostate tumor or
tissue at the termination of the experiment. Tumor tissue was analyzed for modulation of various signaling molecules.
Results: We show that Nexrutine significantly suppressed palpable tumors and progression of cancer in the TRAMP model. Expression
of total and phosphorylated Akt, CREB, and cyclin D1 was significantly reduced in prostate tissue from Nexrutine intervention
group compared with tumors from control animals. Nexrutine also inhibited cyclin D1 transcriptional activity in androgen-independent
PC-3 cells. Overexpression of kinase dead Akt mutant or phosphorylation-defective CREB inhibited cyclin D1 transcriptional
activity.
Conclusions: The current study shows that Nexrutine-mediated targeting of Akt/CREB–induced activation of cyclin D1 prevents the progression
of prostate cancer. Expression of CREB and phosphorylated CREB increased in human prostate tumors compared with normal tissue,
suggesting their potential use as prognostic markers.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.CCR-06-2974</identifier><identifier>PMID: 17473212</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject><![CDATA[Adenocarcinoma - drug therapy ; Adenocarcinoma - pathology ; Adenocarcinoma - prevention & control ; Akt ; Animals ; Antineoplastic agents ; Biological and medical sciences ; Cell Proliferation - drug effects ; CREB ; Cyclic AMP Response Element-Binding Protein - analysis ; Cyclic AMP Response Element-Binding Protein - antagonists & inhibitors ; Cyclic AMP Response Element-Binding Protein - metabolism ; cyclin D1 ; Cyclin D1 - analysis ; Cyclin D1 - antagonists & inhibitors ; Cyclin D1 - metabolism ; Dietary Supplements ; Disease Models, Animal ; Gynecology. Andrology. Obstetrics ; imaging ; in vivo ; Male ; Male genital diseases ; Medical sciences ; Mice ; Mice, Transgenic ; Nephrology. Urinary tract diseases ; Nexrutine ; Pharmacology. Drug treatments ; Phellodendron ; Phosphorylation ; Plant Extracts - administration & dosage ; prostate carcinogenesis ; Prostatic Neoplasms - drug therapy ; Prostatic Neoplasms - pathology ; Prostatic Neoplasms - prevention & control ; Proto-Oncogene Proteins c-akt - analysis ; Proto-Oncogene Proteins c-akt - antagonists & inhibitors ; Proto-Oncogene Proteins c-akt - metabolism ; Receptors, Tumor Necrosis Factor, Member 25 - genetics ; TRAMP model ; Tumors ; Tumors of the urinary system ; Urinary tract. Prostate gland]]></subject><ispartof>Clinical cancer research, 2007-05, Vol.13 (9), p.2784-2794</ispartof><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c448t-b40a53914c652553d13b4bb5ca5ffa48844d1371718e9c5e2c09f94909f7d8f43</citedby><cites>FETCH-LOGICAL-c448t-b40a53914c652553d13b4bb5ca5ffa48844d1371718e9c5e2c09f94909f7d8f43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3343,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18794297$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17473212$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>KUMAR, Addanki P</creatorcontrib><creatorcontrib>BHASKARAN, Shylesh</creatorcontrib><creatorcontrib>GANAPATHY, Manonmani</creatorcontrib><creatorcontrib>CROSBY, Katherine</creatorcontrib><creatorcontrib>DAVIS, Michael D</creatorcontrib><creatorcontrib>KOCHUNOV, Peter</creatorcontrib><creatorcontrib>SCHOOLFIELD, John</creatorcontrib><creatorcontrib>YEH, I-Tien</creatorcontrib><creatorcontrib>TROYER, Dean A</creatorcontrib><creatorcontrib>GHOSH, Rita</creatorcontrib><title>Akt/cAMP-Responsive Element Binding Protein/Cyclin D1 Network: A Novel Target for Prostate Cancer Inhibition in Transgenic Adenocarcinoma of Mouse Prostate Model Mediated by Nexrutine, a Phellodendron Amurense Bark Extract</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Purpose: Development of prostate cancer prevention strategies is an important priority to overcome high incidence, morbidity, and
mortality. Recently, we showed that Nexrutine, an herbal extract, inhibits prostate cancer cell proliferation through modulation
of Akt and cAMP-responsive element binding protein (CREB)–mediated signaling pathways. However, it is unknown if Nexrutine
can be developed as a dietary supplement for the prevention of prostate cancer. In this study, we used the transgenic adenocarcinoma
of mouse prostate (TRAMP) model to examine the ability of Nexrutine to protect TRAMP mice from developing prostate cancer.
Experimental Design: Eight-week-old TRAMP mice were fed with pelleted diet containing 300 and 600 mg/kg Nexrutine for 20 weeks. Efficacy of Nexrutine
was evaluated by magnetic resonance imaging at 18 and 28 weeks of progression and histologic analysis of prostate tumor or
tissue at the termination of the experiment. Tumor tissue was analyzed for modulation of various signaling molecules.
Results: We show that Nexrutine significantly suppressed palpable tumors and progression of cancer in the TRAMP model. Expression
of total and phosphorylated Akt, CREB, and cyclin D1 was significantly reduced in prostate tissue from Nexrutine intervention
group compared with tumors from control animals. Nexrutine also inhibited cyclin D1 transcriptional activity in androgen-independent
PC-3 cells. Overexpression of kinase dead Akt mutant or phosphorylation-defective CREB inhibited cyclin D1 transcriptional
activity.
Conclusions: The current study shows that Nexrutine-mediated targeting of Akt/CREB–induced activation of cyclin D1 prevents the progression
of prostate cancer. Expression of CREB and phosphorylated CREB increased in human prostate tumors compared with normal tissue,
suggesting their potential use as prognostic markers.</description><subject>Adenocarcinoma - drug therapy</subject><subject>Adenocarcinoma - pathology</subject><subject>Adenocarcinoma - prevention & control</subject><subject>Akt</subject><subject>Animals</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Cell Proliferation - drug effects</subject><subject>CREB</subject><subject>Cyclic AMP Response Element-Binding Protein - analysis</subject><subject>Cyclic AMP Response Element-Binding Protein - antagonists & inhibitors</subject><subject>Cyclic AMP Response Element-Binding Protein - metabolism</subject><subject>cyclin D1</subject><subject>Cyclin D1 - analysis</subject><subject>Cyclin D1 - antagonists & inhibitors</subject><subject>Cyclin D1 - metabolism</subject><subject>Dietary Supplements</subject><subject>Disease Models, Animal</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>imaging</subject><subject>in vivo</subject><subject>Male</subject><subject>Male genital diseases</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Nephrology. Urinary tract diseases</subject><subject>Nexrutine</subject><subject>Pharmacology. Drug treatments</subject><subject>Phellodendron</subject><subject>Phosphorylation</subject><subject>Plant Extracts - administration & dosage</subject><subject>prostate carcinogenesis</subject><subject>Prostatic Neoplasms - drug therapy</subject><subject>Prostatic Neoplasms - pathology</subject><subject>Prostatic Neoplasms - prevention & control</subject><subject>Proto-Oncogene Proteins c-akt - analysis</subject><subject>Proto-Oncogene Proteins c-akt - antagonists & inhibitors</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Receptors, Tumor Necrosis Factor, Member 25 - genetics</subject><subject>TRAMP model</subject><subject>Tumors</subject><subject>Tumors of the urinary system</subject><subject>Urinary tract. Prostate gland</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkt9u0zAUxiMEYmPwCCDfgLggq53YcbK7LBSYtI5qKteW45y0poldbHdbX5ZnwaVFveTG__T7vmP7O0nyluBLQlg5IZiXKaZ5dtk09yku0qzi9FlyThjjaZ4V7Hlc_2POklfe_8SYUILpy-SMcMrzjGTnye96HSaqns3Te_Aba7x-ADQdYAQT0LU2nTZLNHc2gDaTZqcGbdBngu4gPFq3vkI1urMPMKCFdEsIqLduT_sgA6BGGgUO3ZiVbnXQ1qAoXjhp_BKMVqjuwFglndLGjhLZHs3s1sPJYGa7aD2DTsddh9pdrPvktkEb-IQkmq9gGCJiOhe963HrwET5tXRrNH0KTqrwOnnRy8HDm-N8kfz4Ml0039Lb719vmvo2VZSWIW0pliyvCFUFyxjLO5K3tG2ZkqzvJS1LSuMRJ5yUUCkGmcJVX9Eqjrwre5pfJB8Ovhtnf23BBzFqr-L1pIH4JsExLXBF_w-SquQFw1UE2QFU8Te8g15snB6l2wmCxb4DxD5dsU9XxA4QuBD7Doi6d8cC23aE7qQ6Rh6B90dAeiWHPuahtD9xJa9odIrcxwO30svVo3Yg1N88HXiIma0EyUUlMl7S_A9_n8oD</recordid><startdate>20070501</startdate><enddate>20070501</enddate><creator>KUMAR, Addanki P</creator><creator>BHASKARAN, Shylesh</creator><creator>GANAPATHY, Manonmani</creator><creator>CROSBY, Katherine</creator><creator>DAVIS, Michael D</creator><creator>KOCHUNOV, Peter</creator><creator>SCHOOLFIELD, John</creator><creator>YEH, I-Tien</creator><creator>TROYER, Dean A</creator><creator>GHOSH, Rita</creator><general>American Association for Cancer Research</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7TO</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20070501</creationdate><title>Akt/cAMP-Responsive Element Binding Protein/Cyclin D1 Network: A Novel Target for Prostate Cancer Inhibition in Transgenic Adenocarcinoma of Mouse Prostate Model Mediated by Nexrutine, a Phellodendron Amurense Bark Extract</title><author>KUMAR, Addanki P ; BHASKARAN, Shylesh ; GANAPATHY, Manonmani ; CROSBY, Katherine ; DAVIS, Michael D ; KOCHUNOV, Peter ; SCHOOLFIELD, John ; YEH, I-Tien ; TROYER, Dean A ; GHOSH, Rita</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c448t-b40a53914c652553d13b4bb5ca5ffa48844d1371718e9c5e2c09f94909f7d8f43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Adenocarcinoma - drug therapy</topic><topic>Adenocarcinoma - pathology</topic><topic>Adenocarcinoma - prevention & control</topic><topic>Akt</topic><topic>Animals</topic><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>Cell Proliferation - drug effects</topic><topic>CREB</topic><topic>Cyclic AMP Response Element-Binding Protein - analysis</topic><topic>Cyclic AMP Response Element-Binding Protein - antagonists & inhibitors</topic><topic>Cyclic AMP Response Element-Binding Protein - metabolism</topic><topic>cyclin D1</topic><topic>Cyclin D1 - analysis</topic><topic>Cyclin D1 - antagonists & inhibitors</topic><topic>Cyclin D1 - metabolism</topic><topic>Dietary Supplements</topic><topic>Disease Models, Animal</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>imaging</topic><topic>in vivo</topic><topic>Male</topic><topic>Male genital diseases</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Nephrology. Urinary tract diseases</topic><topic>Nexrutine</topic><topic>Pharmacology. Drug treatments</topic><topic>Phellodendron</topic><topic>Phosphorylation</topic><topic>Plant Extracts - administration & dosage</topic><topic>prostate carcinogenesis</topic><topic>Prostatic Neoplasms - drug therapy</topic><topic>Prostatic Neoplasms - pathology</topic><topic>Prostatic Neoplasms - prevention & control</topic><topic>Proto-Oncogene Proteins c-akt - analysis</topic><topic>Proto-Oncogene Proteins c-akt - antagonists & inhibitors</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Receptors, Tumor Necrosis Factor, Member 25 - genetics</topic><topic>TRAMP model</topic><topic>Tumors</topic><topic>Tumors of the urinary system</topic><topic>Urinary tract. Prostate gland</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>KUMAR, Addanki P</creatorcontrib><creatorcontrib>BHASKARAN, Shylesh</creatorcontrib><creatorcontrib>GANAPATHY, Manonmani</creatorcontrib><creatorcontrib>CROSBY, Katherine</creatorcontrib><creatorcontrib>DAVIS, Michael D</creatorcontrib><creatorcontrib>KOCHUNOV, Peter</creatorcontrib><creatorcontrib>SCHOOLFIELD, John</creatorcontrib><creatorcontrib>YEH, I-Tien</creatorcontrib><creatorcontrib>TROYER, Dean A</creatorcontrib><creatorcontrib>GHOSH, Rita</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>KUMAR, Addanki P</au><au>BHASKARAN, Shylesh</au><au>GANAPATHY, Manonmani</au><au>CROSBY, Katherine</au><au>DAVIS, Michael D</au><au>KOCHUNOV, Peter</au><au>SCHOOLFIELD, John</au><au>YEH, I-Tien</au><au>TROYER, Dean A</au><au>GHOSH, Rita</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Akt/cAMP-Responsive Element Binding Protein/Cyclin D1 Network: A Novel Target for Prostate Cancer Inhibition in Transgenic Adenocarcinoma of Mouse Prostate Model Mediated by Nexrutine, a Phellodendron Amurense Bark Extract</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2007-05-01</date><risdate>2007</risdate><volume>13</volume><issue>9</issue><spage>2784</spage><epage>2794</epage><pages>2784-2794</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>Purpose: Development of prostate cancer prevention strategies is an important priority to overcome high incidence, morbidity, and
mortality. Recently, we showed that Nexrutine, an herbal extract, inhibits prostate cancer cell proliferation through modulation
of Akt and cAMP-responsive element binding protein (CREB)–mediated signaling pathways. However, it is unknown if Nexrutine
can be developed as a dietary supplement for the prevention of prostate cancer. In this study, we used the transgenic adenocarcinoma
of mouse prostate (TRAMP) model to examine the ability of Nexrutine to protect TRAMP mice from developing prostate cancer.
Experimental Design: Eight-week-old TRAMP mice were fed with pelleted diet containing 300 and 600 mg/kg Nexrutine for 20 weeks. Efficacy of Nexrutine
was evaluated by magnetic resonance imaging at 18 and 28 weeks of progression and histologic analysis of prostate tumor or
tissue at the termination of the experiment. Tumor tissue was analyzed for modulation of various signaling molecules.
Results: We show that Nexrutine significantly suppressed palpable tumors and progression of cancer in the TRAMP model. Expression
of total and phosphorylated Akt, CREB, and cyclin D1 was significantly reduced in prostate tissue from Nexrutine intervention
group compared with tumors from control animals. Nexrutine also inhibited cyclin D1 transcriptional activity in androgen-independent
PC-3 cells. Overexpression of kinase dead Akt mutant or phosphorylation-defective CREB inhibited cyclin D1 transcriptional
activity.
Conclusions: The current study shows that Nexrutine-mediated targeting of Akt/CREB–induced activation of cyclin D1 prevents the progression
of prostate cancer. Expression of CREB and phosphorylated CREB increased in human prostate tumors compared with normal tissue,
suggesting their potential use as prognostic markers.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>17473212</pmid><doi>10.1158/1078-0432.CCR-06-2974</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1078-0432 |
| ispartof | Clinical cancer research, 2007-05, Vol.13 (9), p.2784-2794 |
| issn | 1078-0432 1557-3265 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_70460944 |
| source | MEDLINE; American Association for Cancer Research; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Adenocarcinoma - drug therapy Adenocarcinoma - pathology Adenocarcinoma - prevention & control Akt Animals Antineoplastic agents Biological and medical sciences Cell Proliferation - drug effects CREB Cyclic AMP Response Element-Binding Protein - analysis Cyclic AMP Response Element-Binding Protein - antagonists & inhibitors Cyclic AMP Response Element-Binding Protein - metabolism cyclin D1 Cyclin D1 - analysis Cyclin D1 - antagonists & inhibitors Cyclin D1 - metabolism Dietary Supplements Disease Models, Animal Gynecology. Andrology. Obstetrics imaging in vivo Male Male genital diseases Medical sciences Mice Mice, Transgenic Nephrology. Urinary tract diseases Nexrutine Pharmacology. Drug treatments Phellodendron Phosphorylation Plant Extracts - administration & dosage prostate carcinogenesis Prostatic Neoplasms - drug therapy Prostatic Neoplasms - pathology Prostatic Neoplasms - prevention & control Proto-Oncogene Proteins c-akt - analysis Proto-Oncogene Proteins c-akt - antagonists & inhibitors Proto-Oncogene Proteins c-akt - metabolism Receptors, Tumor Necrosis Factor, Member 25 - genetics TRAMP model Tumors Tumors of the urinary system Urinary tract. Prostate gland |
| title | Akt/cAMP-Responsive Element Binding Protein/Cyclin D1 Network: A Novel Target for Prostate Cancer Inhibition in Transgenic Adenocarcinoma of Mouse Prostate Model Mediated by Nexrutine, a Phellodendron Amurense Bark Extract |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-10T05%3A14%3A14IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Akt/cAMP-Responsive%20Element%20Binding%20Protein/Cyclin%20D1%20Network:%20A%20Novel%20Target%20for%20Prostate%20Cancer%20Inhibition%20in%20Transgenic%20Adenocarcinoma%20of%20Mouse%20Prostate%20Model%20Mediated%20by%20Nexrutine,%20a%20Phellodendron%20Amurense%20Bark%20Extract&rft.jtitle=Clinical%20cancer%20research&rft.au=KUMAR,%20Addanki%20P&rft.date=2007-05-01&rft.volume=13&rft.issue=9&rft.spage=2784&rft.epage=2794&rft.pages=2784-2794&rft.issn=1078-0432&rft.eissn=1557-3265&rft_id=info:doi/10.1158/1078-0432.CCR-06-2974&rft_dat=%3Cproquest_cross%3E70460944%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=19876509&rft_id=info:pmid/17473212&rfr_iscdi=true |