Selective induction of cell cycle arrest and apoptosis in human prostate cancer cells through adenoviral transfer of the melanoma differentiation-associated −7 (mda-7)/interleukin-24 (IL-24) gene
We have previously reported that overexpression of the melanoma differentiation-associated gene -7 ( mda-7 ) using a replication-defective adenovirus (Ad-mda7), results in tumor-specific growth suppression and induction of apoptosis in wide variety of cancer cells. In the present study, we investiga...
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| Veröffentlicht in: | Cancer gene therapy 2005-03, Vol.12 (3), p.238-247 |
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| creator | Saito, Yuji Miyahara, Ryo Gopalan, Began Litvak, Anya Inoue, Satoshi Shanker, Manish Branch, Cynthia D Mhashilkar, Abner M Roth, Jack A Chada, Sunil Ramesh, Rajagopal |
| description | We have previously reported that overexpression of the melanoma differentiation-associated gene -7 (
mda-7
) using a replication-defective adenovirus (Ad-mda7), results in tumor-specific growth suppression and induction of apoptosis in wide variety of cancer cells. In the present study, we investigated the antitumor activity of Ad-mda7 and the underlying mechanism in human prostate cancer cells and normal prostate epithelial cells. Overexpression of MDA-7 induced significant (
P
=.001) suppression of cell growth and apoptosis in prostate cancer cells (DU 145, LNCaP, and PC-3). In normal prostate epithelial cells (PrEC) some degree of growth inhibition but not apoptosis was observed. However, the inhibitory effects in normal cells were less compared to tumor cells. Growth inhibitory effects were mediated by the intracellular and not by extracellular MDA-7 protein. Molecular effectors that are involved in Ad-mda7-mediated tumor killing included activation of the caspase cascade, and the induction of G2 phase cell cycle arrest through the inhibition of Cdc25C pathway. These results demonstrate the mechanisms by which Ad-mda7 exerts its antitumor activity in human prostate cancer cells. The antitumor activity combined with previously reported antiangiogenic and proimmune properties of Ad-mda7 can serve as a potential therapeutic agent for treatment of primary and disseminated prostate cancer. |
| doi_str_mv | 10.1038/sj.cgt.7700780 |
| format | Article |
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mda-7
) using a replication-defective adenovirus (Ad-mda7), results in tumor-specific growth suppression and induction of apoptosis in wide variety of cancer cells. In the present study, we investigated the antitumor activity of Ad-mda7 and the underlying mechanism in human prostate cancer cells and normal prostate epithelial cells. Overexpression of MDA-7 induced significant (
P
=.001) suppression of cell growth and apoptosis in prostate cancer cells (DU 145, LNCaP, and PC-3). In normal prostate epithelial cells (PrEC) some degree of growth inhibition but not apoptosis was observed. However, the inhibitory effects in normal cells were less compared to tumor cells. Growth inhibitory effects were mediated by the intracellular and not by extracellular MDA-7 protein. Molecular effectors that are involved in Ad-mda7-mediated tumor killing included activation of the caspase cascade, and the induction of G2 phase cell cycle arrest through the inhibition of Cdc25C pathway. These results demonstrate the mechanisms by which Ad-mda7 exerts its antitumor activity in human prostate cancer cells. The antitumor activity combined with previously reported antiangiogenic and proimmune properties of Ad-mda7 can serve as a potential therapeutic agent for treatment of primary and disseminated prostate cancer.</description><identifier>ISSN: 0929-1903</identifier><identifier>EISSN: 1476-5500</identifier><identifier>DOI: 10.1038/sj.cgt.7700780</identifier><identifier>PMID: 15578066</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Adenoviridae ; Adenovirus ; Analysis of Variance ; Annexin A5 - metabolism ; Antitumor activity ; Apoptosis ; Apoptosis - drug effects ; Apoptosis - genetics ; Biomedical and Life Sciences ; Biomedicine ; Care and treatment ; Caspase ; Cell cycle ; Cell Cycle - drug effects ; Cell Cycle - genetics ; Cell Proliferation ; Diagnosis ; Epithelial cells ; Flow Cytometry ; G2 phase ; Gene Expression ; Gene Expression Regulation, Neoplastic - drug effects ; Gene Therapy ; Gene Transfer Techniques ; Genes, Tumor Suppressor ; Genetic aspects ; Genetic Therapy - methods ; Genetic Vectors ; Humans ; Immunoblotting ; Interleukin 24 ; Interleukins ; Interleukins - genetics ; Interleukins - pharmacology ; Male ; Mda-7 protein ; Melanoma ; original-article ; Physiological aspects ; Prostate cancer ; Prostatic Neoplasms - therapy ; Risk factors ; Tumor cells ; Tumor Cells, Cultured</subject><ispartof>Cancer gene therapy, 2005-03, Vol.12 (3), p.238-247</ispartof><rights>Springer Nature America, Inc. 2005</rights><rights>COPYRIGHT 2005 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Mar 2005</rights><rights>Nature Publishing Group 2005.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c556t-e756e116272d3a9f7b8c97df4c9a5e610c8c54edde737ee44aa49d31be0003a83</citedby><cites>FETCH-LOGICAL-c556t-e756e116272d3a9f7b8c97df4c9a5e610c8c54edde737ee44aa49d31be0003a83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/sj.cgt.7700780$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/sj.cgt.7700780$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15578066$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Saito, Yuji</creatorcontrib><creatorcontrib>Miyahara, Ryo</creatorcontrib><creatorcontrib>Gopalan, Began</creatorcontrib><creatorcontrib>Litvak, Anya</creatorcontrib><creatorcontrib>Inoue, Satoshi</creatorcontrib><creatorcontrib>Shanker, Manish</creatorcontrib><creatorcontrib>Branch, Cynthia D</creatorcontrib><creatorcontrib>Mhashilkar, Abner M</creatorcontrib><creatorcontrib>Roth, Jack A</creatorcontrib><creatorcontrib>Chada, Sunil</creatorcontrib><creatorcontrib>Ramesh, Rajagopal</creatorcontrib><title>Selective induction of cell cycle arrest and apoptosis in human prostate cancer cells through adenoviral transfer of the melanoma differentiation-associated −7 (mda-7)/interleukin-24 (IL-24) gene</title><title>Cancer gene therapy</title><addtitle>Cancer Gene Ther</addtitle><addtitle>Cancer Gene Ther</addtitle><description>We have previously reported that overexpression of the melanoma differentiation-associated gene -7 (
mda-7
) using a replication-defective adenovirus (Ad-mda7), results in tumor-specific growth suppression and induction of apoptosis in wide variety of cancer cells. In the present study, we investigated the antitumor activity of Ad-mda7 and the underlying mechanism in human prostate cancer cells and normal prostate epithelial cells. Overexpression of MDA-7 induced significant (
P
=.001) suppression of cell growth and apoptosis in prostate cancer cells (DU 145, LNCaP, and PC-3). In normal prostate epithelial cells (PrEC) some degree of growth inhibition but not apoptosis was observed. However, the inhibitory effects in normal cells were less compared to tumor cells. Growth inhibitory effects were mediated by the intracellular and not by extracellular MDA-7 protein. Molecular effectors that are involved in Ad-mda7-mediated tumor killing included activation of the caspase cascade, and the induction of G2 phase cell cycle arrest through the inhibition of Cdc25C pathway. These results demonstrate the mechanisms by which Ad-mda7 exerts its antitumor activity in human prostate cancer cells. The antitumor activity combined with previously reported antiangiogenic and proimmune properties of Ad-mda7 can serve as a potential therapeutic agent for treatment of primary and disseminated prostate cancer.</description><subject>Adenoviridae</subject><subject>Adenovirus</subject><subject>Analysis of Variance</subject><subject>Annexin A5 - metabolism</subject><subject>Antitumor activity</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Apoptosis - genetics</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Care and treatment</subject><subject>Caspase</subject><subject>Cell cycle</subject><subject>Cell Cycle - drug effects</subject><subject>Cell Cycle - genetics</subject><subject>Cell Proliferation</subject><subject>Diagnosis</subject><subject>Epithelial cells</subject><subject>Flow Cytometry</subject><subject>G2 phase</subject><subject>Gene Expression</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Gene Therapy</subject><subject>Gene Transfer Techniques</subject><subject>Genes, Tumor Suppressor</subject><subject>Genetic aspects</subject><subject>Genetic Therapy - methods</subject><subject>Genetic Vectors</subject><subject>Humans</subject><subject>Immunoblotting</subject><subject>Interleukin 24</subject><subject>Interleukins</subject><subject>Interleukins - genetics</subject><subject>Interleukins - pharmacology</subject><subject>Male</subject><subject>Mda-7 protein</subject><subject>Melanoma</subject><subject>original-article</subject><subject>Physiological aspects</subject><subject>Prostate cancer</subject><subject>Prostatic Neoplasms - therapy</subject><subject>Risk factors</subject><subject>Tumor cells</subject><subject>Tumor Cells, Cultured</subject><issn>0929-1903</issn><issn>1476-5500</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFks2KFDEQxxtR3HX16lGCguweeiZf3ek-LosfCwMe1HOoSaqne-xOxiS9sG_g2XfyRXwSM87AgLB4qiL1q8_8i-IlowtGRbOM24XZpIVSlKqGPirOmVR1WVWUPi7OacvbkrVUnBXPYtxSmoNKPC3OWFVluq7Pi1-fcUSThjskg7Nz9rwjviMGx5GYezMigRAwJgLOEtj5XfJxiBkm_TyBI7vgY4KExIAzGP4mRpL64OdNT8Ci83dDgJGkAC52mcjVU49kwhGcn4DYocvP6NIA--4lxOhN9tGS3z9-KnI5WSjV1XJwCcOI87fBlVySy9tVNldkgw6fF086GCO-ONqL4uv7d19uPparTx9ub65XpamqOpWoqhoZq7niVkDbqXVjWmU7aVqosGbUNKaSaC0qoRClBJCtFWyNlFIBjbgo3h7q5q2_z_kqehrifmNw6OeoayVFS9v2vyBTjeQt5xl88w-49XNweQnNa8kUY4KrTL1-kGKqolLw-tRzAyPqHmFMffTjvD9q1Nes4bUSlWQZXBxAk_8uBuz0LgwThHvNqN6rSsetzqrSR1XlhFfH9vN6QnvCjzLKwPIAxBxyGwyn-R4o-QfVUtql</recordid><startdate>20050301</startdate><enddate>20050301</enddate><creator>Saito, Yuji</creator><creator>Miyahara, Ryo</creator><creator>Gopalan, Began</creator><creator>Litvak, Anya</creator><creator>Inoue, Satoshi</creator><creator>Shanker, Manish</creator><creator>Branch, Cynthia D</creator><creator>Mhashilkar, Abner M</creator><creator>Roth, Jack A</creator><creator>Chada, Sunil</creator><creator>Ramesh, Rajagopal</creator><general>Nature Publishing Group US</general><general>Nature Publishing Group</general><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>3V.</scope><scope>7QP</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7QO</scope><scope>7X8</scope></search><sort><creationdate>20050301</creationdate><title>Selective induction of cell cycle arrest and apoptosis in human prostate cancer cells through adenoviral transfer of the melanoma differentiation-associated −7 (mda-7)/interleukin-24 (IL-24) gene</title><author>Saito, Yuji ; Miyahara, Ryo ; Gopalan, Began ; Litvak, Anya ; Inoue, Satoshi ; Shanker, Manish ; Branch, Cynthia D ; Mhashilkar, Abner M ; Roth, Jack A ; Chada, Sunil ; Ramesh, Rajagopal</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c556t-e756e116272d3a9f7b8c97df4c9a5e610c8c54edde737ee44aa49d31be0003a83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Adenoviridae</topic><topic>Adenovirus</topic><topic>Analysis of Variance</topic><topic>Annexin A5 - metabolism</topic><topic>Antitumor activity</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Apoptosis - genetics</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Care and treatment</topic><topic>Caspase</topic><topic>Cell cycle</topic><topic>Cell Cycle - drug effects</topic><topic>Cell Cycle - genetics</topic><topic>Cell Proliferation</topic><topic>Diagnosis</topic><topic>Epithelial cells</topic><topic>Flow Cytometry</topic><topic>G2 phase</topic><topic>Gene Expression</topic><topic>Gene Expression Regulation, Neoplastic - drug effects</topic><topic>Gene Therapy</topic><topic>Gene Transfer Techniques</topic><topic>Genes, Tumor Suppressor</topic><topic>Genetic aspects</topic><topic>Genetic Therapy - methods</topic><topic>Genetic Vectors</topic><topic>Humans</topic><topic>Immunoblotting</topic><topic>Interleukin 24</topic><topic>Interleukins</topic><topic>Interleukins - genetics</topic><topic>Interleukins - pharmacology</topic><topic>Male</topic><topic>Mda-7 protein</topic><topic>Melanoma</topic><topic>original-article</topic><topic>Physiological aspects</topic><topic>Prostate cancer</topic><topic>Prostatic Neoplasms - therapy</topic><topic>Risk factors</topic><topic>Tumor cells</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Saito, Yuji</creatorcontrib><creatorcontrib>Miyahara, Ryo</creatorcontrib><creatorcontrib>Gopalan, Began</creatorcontrib><creatorcontrib>Litvak, Anya</creatorcontrib><creatorcontrib>Inoue, Satoshi</creatorcontrib><creatorcontrib>Shanker, Manish</creatorcontrib><creatorcontrib>Branch, Cynthia D</creatorcontrib><creatorcontrib>Mhashilkar, Abner M</creatorcontrib><creatorcontrib>Roth, Jack A</creatorcontrib><creatorcontrib>Chada, Sunil</creatorcontrib><creatorcontrib>Ramesh, Rajagopal</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Cancer gene therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Saito, Yuji</au><au>Miyahara, Ryo</au><au>Gopalan, Began</au><au>Litvak, Anya</au><au>Inoue, Satoshi</au><au>Shanker, Manish</au><au>Branch, Cynthia D</au><au>Mhashilkar, Abner M</au><au>Roth, Jack A</au><au>Chada, Sunil</au><au>Ramesh, Rajagopal</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Selective induction of cell cycle arrest and apoptosis in human prostate cancer cells through adenoviral transfer of the melanoma differentiation-associated −7 (mda-7)/interleukin-24 (IL-24) gene</atitle><jtitle>Cancer gene therapy</jtitle><stitle>Cancer Gene Ther</stitle><addtitle>Cancer Gene Ther</addtitle><date>2005-03-01</date><risdate>2005</risdate><volume>12</volume><issue>3</issue><spage>238</spage><epage>247</epage><pages>238-247</pages><issn>0929-1903</issn><eissn>1476-5500</eissn><abstract>We have previously reported that overexpression of the melanoma differentiation-associated gene -7 (
mda-7
) using a replication-defective adenovirus (Ad-mda7), results in tumor-specific growth suppression and induction of apoptosis in wide variety of cancer cells. In the present study, we investigated the antitumor activity of Ad-mda7 and the underlying mechanism in human prostate cancer cells and normal prostate epithelial cells. Overexpression of MDA-7 induced significant (
P
=.001) suppression of cell growth and apoptosis in prostate cancer cells (DU 145, LNCaP, and PC-3). In normal prostate epithelial cells (PrEC) some degree of growth inhibition but not apoptosis was observed. However, the inhibitory effects in normal cells were less compared to tumor cells. Growth inhibitory effects were mediated by the intracellular and not by extracellular MDA-7 protein. Molecular effectors that are involved in Ad-mda7-mediated tumor killing included activation of the caspase cascade, and the induction of G2 phase cell cycle arrest through the inhibition of Cdc25C pathway. These results demonstrate the mechanisms by which Ad-mda7 exerts its antitumor activity in human prostate cancer cells. The antitumor activity combined with previously reported antiangiogenic and proimmune properties of Ad-mda7 can serve as a potential therapeutic agent for treatment of primary and disseminated prostate cancer.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>15578066</pmid><doi>10.1038/sj.cgt.7700780</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0929-1903 |
| ispartof | Cancer gene therapy, 2005-03, Vol.12 (3), p.238-247 |
| issn | 0929-1903 1476-5500 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_67439099 |
| source | MEDLINE; SpringerLink Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Adenoviridae Adenovirus Analysis of Variance Annexin A5 - metabolism Antitumor activity Apoptosis Apoptosis - drug effects Apoptosis - genetics Biomedical and Life Sciences Biomedicine Care and treatment Caspase Cell cycle Cell Cycle - drug effects Cell Cycle - genetics Cell Proliferation Diagnosis Epithelial cells Flow Cytometry G2 phase Gene Expression Gene Expression Regulation, Neoplastic - drug effects Gene Therapy Gene Transfer Techniques Genes, Tumor Suppressor Genetic aspects Genetic Therapy - methods Genetic Vectors Humans Immunoblotting Interleukin 24 Interleukins Interleukins - genetics Interleukins - pharmacology Male Mda-7 protein Melanoma original-article Physiological aspects Prostate cancer Prostatic Neoplasms - therapy Risk factors Tumor cells Tumor Cells, Cultured |
| title | Selective induction of cell cycle arrest and apoptosis in human prostate cancer cells through adenoviral transfer of the melanoma differentiation-associated −7 (mda-7)/interleukin-24 (IL-24) gene |
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