A survivin double point mutant has potent inhibitory effect on the growth of hepatocellular cancer cells
Survivin is an attractive target in cancer therapy. Previous studies have demonstrated that survivin dominant-negative mutants T34A and C84A were able to induce apoptosis in cancer cells. Given that they had different mechanisms in inducing apoptosis, our study was undertaken to determine whether a...
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| Veröffentlicht in: | Cancer biology & therapy 2008-04, Vol.7 (4), p.547-554 |
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| creator | Zhang, Rui Wang, Tao Li, Kai-Nan Qin, Wei-Wei Chen, Rui Wang, Kai Jia, Lin-Tao Zhao, Jing Wen, Wei-Hong Meng, Yan-Ling Yao, Li-Bo Yang, An-Gang |
| description | Survivin is an attractive target in cancer therapy. Previous studies have demonstrated that survivin dominant-negative mutants T34A and C84A were able to induce apoptosis in cancer cells. Given that they had different mechanisms in inducing apoptosis, our study was undertaken to determine whether a survivin double point mutant (TC34,84AA) could achieve more potent inhibitory effect on the growth of hepatocellular cancer cells. Adenoviruses expressing survivin mutants were constructed and transduced into hepatocellular cancer cells. The inhibitory effect of the survivin mutants on cancer cell growth was measured. Transduction of cancer cells with all three survivin mutants resulted in significant apoptosis. Compared with survivin mutants T34A or C84A alone, the cancer killing effect of survivin TC34,84AA was much stronger. In addition, the survivin mutants were more sensitive than wild type survivin to the degradation in the ubiquitin-proteasome pathway. Our results suggest that adenovirus-delivered dominant-negative survivin TC34,84AA promotes apoptosis-mediated hepatocellular carcinoma suppression, and could potentially be a promising candidate for cancer therapies. |
| doi_str_mv | 10.4161/cbt.7.4.5484 |
| format | Article |
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Previous studies have demonstrated that survivin dominant-negative mutants T34A and C84A were able to induce apoptosis in cancer cells. Given that they had different mechanisms in inducing apoptosis, our study was undertaken to determine whether a survivin double point mutant (TC34,84AA) could achieve more potent inhibitory effect on the growth of hepatocellular cancer cells. Adenoviruses expressing survivin mutants were constructed and transduced into hepatocellular cancer cells. The inhibitory effect of the survivin mutants on cancer cell growth was measured. Transduction of cancer cells with all three survivin mutants resulted in significant apoptosis. Compared with survivin mutants T34A or C84A alone, the cancer killing effect of survivin TC34,84AA was much stronger. In addition, the survivin mutants were more sensitive than wild type survivin to the degradation in the ubiquitin-proteasome pathway. Our results suggest that adenovirus-delivered dominant-negative survivin TC34,84AA promotes apoptosis-mediated hepatocellular carcinoma suppression, and could potentially be a promising candidate for cancer therapies.</description><identifier>ISSN: 1538-4047</identifier><identifier>EISSN: 1555-8576</identifier><identifier>DOI: 10.4161/cbt.7.4.5484</identifier><identifier>PMID: 18296918</identifier><language>eng</language><publisher>United States: Taylor & Francis</publisher><subject>Adenoviridae ; Apoptosis ; Binding ; Biology ; Bioscience ; Calcium ; Cancer ; Carcinoma, Hepatocellular - therapy ; Cell ; Cell Line, Tumor ; Cell Proliferation ; Cycle ; Genetic Therapy ; Genetic Vectors ; Humans ; Inhibitor of Apoptosis Proteins ; Landes ; Liver Neoplasms - therapy ; Microtubule-Associated Proteins - genetics ; Neoplasm Proteins - genetics ; Organogenesis ; Point Mutation ; Proteins ; Survivin</subject><ispartof>Cancer biology & therapy, 2008-04, Vol.7 (4), p.547-554</ispartof><rights>Copyright © 2008 Landes Bioscience 2008</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c416t-e2b45c430a13e73aa025c6691cc90628661e10b609cdd69f88746ea5d2e1b1223</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18296918$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Rui</creatorcontrib><creatorcontrib>Wang, Tao</creatorcontrib><creatorcontrib>Li, Kai-Nan</creatorcontrib><creatorcontrib>Qin, Wei-Wei</creatorcontrib><creatorcontrib>Chen, Rui</creatorcontrib><creatorcontrib>Wang, Kai</creatorcontrib><creatorcontrib>Jia, Lin-Tao</creatorcontrib><creatorcontrib>Zhao, Jing</creatorcontrib><creatorcontrib>Wen, Wei-Hong</creatorcontrib><creatorcontrib>Meng, Yan-Ling</creatorcontrib><creatorcontrib>Yao, Li-Bo</creatorcontrib><creatorcontrib>Yang, An-Gang</creatorcontrib><title>A survivin double point mutant has potent inhibitory effect on the growth of hepatocellular cancer cells</title><title>Cancer biology & therapy</title><addtitle>Cancer Biol Ther</addtitle><description>Survivin is an attractive target in cancer therapy. Previous studies have demonstrated that survivin dominant-negative mutants T34A and C84A were able to induce apoptosis in cancer cells. Given that they had different mechanisms in inducing apoptosis, our study was undertaken to determine whether a survivin double point mutant (TC34,84AA) could achieve more potent inhibitory effect on the growth of hepatocellular cancer cells. Adenoviruses expressing survivin mutants were constructed and transduced into hepatocellular cancer cells. The inhibitory effect of the survivin mutants on cancer cell growth was measured. Transduction of cancer cells with all three survivin mutants resulted in significant apoptosis. Compared with survivin mutants T34A or C84A alone, the cancer killing effect of survivin TC34,84AA was much stronger. In addition, the survivin mutants were more sensitive than wild type survivin to the degradation in the ubiquitin-proteasome pathway. Our results suggest that adenovirus-delivered dominant-negative survivin TC34,84AA promotes apoptosis-mediated hepatocellular carcinoma suppression, and could potentially be a promising candidate for cancer therapies.</description><subject>Adenoviridae</subject><subject>Apoptosis</subject><subject>Binding</subject><subject>Biology</subject><subject>Bioscience</subject><subject>Calcium</subject><subject>Cancer</subject><subject>Carcinoma, Hepatocellular - therapy</subject><subject>Cell</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation</subject><subject>Cycle</subject><subject>Genetic Therapy</subject><subject>Genetic Vectors</subject><subject>Humans</subject><subject>Inhibitor of Apoptosis Proteins</subject><subject>Landes</subject><subject>Liver Neoplasms - therapy</subject><subject>Microtubule-Associated Proteins - genetics</subject><subject>Neoplasm Proteins - genetics</subject><subject>Organogenesis</subject><subject>Point Mutation</subject><subject>Proteins</subject><subject>Survivin</subject><issn>1538-4047</issn><issn>1555-8576</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkEtPxCAUhYnROL52rg0rV3YESqFdToyvxMSNrgmltxbTlhGoZv69NDPqxtW5kI9zDwehc0qWnAp6beq4lEu-LHjJ99ARLYoiKwsp9uc5LzNOuFyg4xDeCWGSieoQLWjJKlHR8gh1Kxwm_2k_7YgbN9U94LWzY8TDFHWSTod0ESGNduxsbaPzGwxtCyZiN-LYAX7z7it22LW4g7WOzkDfT7322OjRQJJ0DqfooNV9gLOdnqDXu9uXm4fs6fn-8Wb1lJn0m5gBq3lheE40zUHmWhNWGJGyGlMRwUohKFBSC1KZphFVW5aSC9BFw4DWlLH8BF1ufdfefUwQohpsmBPoEdwUlKhyQiXhCbzagsa7EDy0au3toP1GUaLmZlVqVknF1dxswi92vlM9QPMH76pMANkCaVMDobYuGAupgF909tM-WtPDj6fcPrFj6_ygv5zvGxX1pne-9ak8G1T-b5pvQwOamw</recordid><startdate>20080401</startdate><enddate>20080401</enddate><creator>Zhang, Rui</creator><creator>Wang, Tao</creator><creator>Li, Kai-Nan</creator><creator>Qin, Wei-Wei</creator><creator>Chen, Rui</creator><creator>Wang, Kai</creator><creator>Jia, Lin-Tao</creator><creator>Zhao, Jing</creator><creator>Wen, Wei-Hong</creator><creator>Meng, Yan-Ling</creator><creator>Yao, Li-Bo</creator><creator>Yang, An-Gang</creator><general>Taylor & Francis</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>7X8</scope></search><sort><creationdate>20080401</creationdate><title>A survivin double point mutant has potent inhibitory effect on the growth of hepatocellular cancer cells</title><author>Zhang, Rui ; Wang, Tao ; Li, Kai-Nan ; Qin, Wei-Wei ; Chen, Rui ; Wang, Kai ; Jia, Lin-Tao ; Zhao, Jing ; Wen, Wei-Hong ; Meng, Yan-Ling ; Yao, Li-Bo ; Yang, An-Gang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c416t-e2b45c430a13e73aa025c6691cc90628661e10b609cdd69f88746ea5d2e1b1223</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Adenoviridae</topic><topic>Apoptosis</topic><topic>Binding</topic><topic>Biology</topic><topic>Bioscience</topic><topic>Calcium</topic><topic>Cancer</topic><topic>Carcinoma, Hepatocellular - therapy</topic><topic>Cell</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation</topic><topic>Cycle</topic><topic>Genetic Therapy</topic><topic>Genetic Vectors</topic><topic>Humans</topic><topic>Inhibitor of Apoptosis Proteins</topic><topic>Landes</topic><topic>Liver Neoplasms - therapy</topic><topic>Microtubule-Associated Proteins - genetics</topic><topic>Neoplasm Proteins - genetics</topic><topic>Organogenesis</topic><topic>Point Mutation</topic><topic>Proteins</topic><topic>Survivin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Rui</creatorcontrib><creatorcontrib>Wang, Tao</creatorcontrib><creatorcontrib>Li, Kai-Nan</creatorcontrib><creatorcontrib>Qin, Wei-Wei</creatorcontrib><creatorcontrib>Chen, Rui</creatorcontrib><creatorcontrib>Wang, Kai</creatorcontrib><creatorcontrib>Jia, Lin-Tao</creatorcontrib><creatorcontrib>Zhao, Jing</creatorcontrib><creatorcontrib>Wen, Wei-Hong</creatorcontrib><creatorcontrib>Meng, Yan-Ling</creatorcontrib><creatorcontrib>Yao, Li-Bo</creatorcontrib><creatorcontrib>Yang, An-Gang</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Cancer biology & therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Rui</au><au>Wang, Tao</au><au>Li, Kai-Nan</au><au>Qin, Wei-Wei</au><au>Chen, Rui</au><au>Wang, Kai</au><au>Jia, Lin-Tao</au><au>Zhao, Jing</au><au>Wen, Wei-Hong</au><au>Meng, Yan-Ling</au><au>Yao, Li-Bo</au><au>Yang, An-Gang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A survivin double point mutant has potent inhibitory effect on the growth of hepatocellular cancer cells</atitle><jtitle>Cancer biology & therapy</jtitle><addtitle>Cancer Biol Ther</addtitle><date>2008-04-01</date><risdate>2008</risdate><volume>7</volume><issue>4</issue><spage>547</spage><epage>554</epage><pages>547-554</pages><issn>1538-4047</issn><eissn>1555-8576</eissn><abstract>Survivin is an attractive target in cancer therapy. Previous studies have demonstrated that survivin dominant-negative mutants T34A and C84A were able to induce apoptosis in cancer cells. Given that they had different mechanisms in inducing apoptosis, our study was undertaken to determine whether a survivin double point mutant (TC34,84AA) could achieve more potent inhibitory effect on the growth of hepatocellular cancer cells. Adenoviruses expressing survivin mutants were constructed and transduced into hepatocellular cancer cells. The inhibitory effect of the survivin mutants on cancer cell growth was measured. Transduction of cancer cells with all three survivin mutants resulted in significant apoptosis. Compared with survivin mutants T34A or C84A alone, the cancer killing effect of survivin TC34,84AA was much stronger. In addition, the survivin mutants were more sensitive than wild type survivin to the degradation in the ubiquitin-proteasome pathway. Our results suggest that adenovirus-delivered dominant-negative survivin TC34,84AA promotes apoptosis-mediated hepatocellular carcinoma suppression, and could potentially be a promising candidate for cancer therapies.</abstract><cop>United States</cop><pub>Taylor & Francis</pub><pmid>18296918</pmid><doi>10.4161/cbt.7.4.5484</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adenoviridae Apoptosis Binding Biology Bioscience Calcium Cancer Carcinoma, Hepatocellular - therapy Cell Cell Line, Tumor Cell Proliferation Cycle Genetic Therapy Genetic Vectors Humans Inhibitor of Apoptosis Proteins Landes Liver Neoplasms - therapy Microtubule-Associated Proteins - genetics Neoplasm Proteins - genetics Organogenesis Point Mutation Proteins Survivin |
| title | A survivin double point mutant has potent inhibitory effect on the growth of hepatocellular cancer cells |
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