Tumor-targeting Salmonella typhimurium, a natural tool for activation of prodrug 6MePdR and their combination therapy in murine melanoma model
The PNP/6-methylpurine 2′-deoxyriboside (6MePdR) system is an efficient gene-directed enzyme prodrug therapy system with significant antitumor activities. In this system, Escherichia coli purine nucleoside phosphorylase (ePNP) activates nontoxic 6MePdR into potent antitumor drug 6-methylpurine (6MeP...
Gespeichert in:
| Veröffentlicht in: | Applied microbiology and biotechnology 2013-05, Vol.97 (10), p.4393-4401 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 4401 |
|---|---|
| container_issue | 10 |
| container_start_page | 4393 |
| container_title | Applied microbiology and biotechnology |
| container_volume | 97 |
| creator | Chen, Guo Tang, Bo Yang, Bing-Ya Chen, Jian-Xiang Zhou, Jia-Hua Li, Jia-Huang Hua, Zi-Chun |
| description | The PNP/6-methylpurine 2′-deoxyriboside (6MePdR) system is an efficient gene-directed enzyme prodrug therapy system with significant antitumor activities. In this system,
Escherichia coli
purine nucleoside phosphorylase (ePNP) activates nontoxic 6MePdR into potent antitumor drug 6-methylpurine (6MeP). The
Salmonella typhimurium
PNP (sPNP) gene has a 96-% sequence homology in comparison with ePNP and also has the ability to convert 6MePdR to 6MeP. In this study, we used tumor-targeting
S. typhimurium
VNP20009 expressing endogenous PNP gene constitutively to activate 6MePdR and a combination treatment of bacteria and prodrug in B16F10 melanoma model. The conversion of 6MePdR to 6MeP by
S. typhimurium
was analyzed by HPLC and the enzyme activity of sPNP was confirmed by in vitro (tetrazolium-based colorimetric assay) MTT cytotoxicity assay. After systemic administration of VNP20009 to mice, the bacteria largely accumulated and specifically delivered endogenous sPNP in the tumor. In comparison with VNP20009 or 6MePdR treatment alone, combined administration of VNP20009 followed by 6MePdR treatment significantly delayed the growth of B16F10 tumor and increased the CD8
+
T-cell infiltration. In summary, our results demonstrated that the combination therapy of
S. typhimurium
and prodrug 6MePdR is a promising strategy for cancer therapy. |
| doi_str_mv | 10.1007/s00253-012-4321-8 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_1356930976</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A337618257</galeid><sourcerecordid>A337618257</sourcerecordid><originalsourceid>FETCH-LOGICAL-c543t-e1c2b36fa9d19ab997c38520022729bb9bcc9e20ba6b7e43c6b7dd61804ecfd53</originalsourceid><addsrcrecordid>eNqNkt1uFSEUhYnR2GP1AbwxJN7UxKn8zMBw2TRVm9Ro2npNGIaZ0gxwBMZ4XqLPLJOpP8doYrjYBL61sjcsAJ5jdIwR4m8SQqShFcKkqinBVfsAbHDZVYjh-iHYIMybijeiPQBPUrpFBWwZewwOSKltS9gG3F3PLsQqqziabP0Ir9TkgjfTpGDebW-sm6Od3WuooFd5jmqCOYQJDiFCpbP9qrINHoYBbmPo4zxC9sF86i-h8j3MN8ZGqIPrrF-5chLVdgeth4uxN9CZSfngFHShN9NT8GhQUzLP7ush-Pz27Pr0fXXx8d356clFpZua5spgTTrKBiV6LFQnBNe0bUh5DsKJ6DrRaS0MQZ1iHTc11aX0PcMtqo0e-oYegqPVt3T9ZTYpS2eTXqb2JsxJYtowQZHg7D_QWnCERb24vvwDvQ1z9GWQxZDjpm4E-0WNajLS-iHkqPRiKk8o5aVL0vBCHf-FKqs3zuryQ4Mt53uCV3uCwmTzLY9qTkmeX13us3hldQwpRTPIbbROxZ3ESC7Rkmu0ZEmMXKIl26J5cT_c3DnT_1T8yFIByAqkcuVHE3-b_p-u3wH3i9hV</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1357154596</pqid></control><display><type>article</type><title>Tumor-targeting Salmonella typhimurium, a natural tool for activation of prodrug 6MePdR and their combination therapy in murine melanoma model</title><source>MEDLINE</source><source>SpringerNature Journals</source><creator>Chen, Guo ; Tang, Bo ; Yang, Bing-Ya ; Chen, Jian-Xiang ; Zhou, Jia-Hua ; Li, Jia-Huang ; Hua, Zi-Chun</creator><creatorcontrib>Chen, Guo ; Tang, Bo ; Yang, Bing-Ya ; Chen, Jian-Xiang ; Zhou, Jia-Hua ; Li, Jia-Huang ; Hua, Zi-Chun</creatorcontrib><description>The PNP/6-methylpurine 2′-deoxyriboside (6MePdR) system is an efficient gene-directed enzyme prodrug therapy system with significant antitumor activities. In this system,
Escherichia coli
purine nucleoside phosphorylase (ePNP) activates nontoxic 6MePdR into potent antitumor drug 6-methylpurine (6MeP). The
Salmonella typhimurium
PNP (sPNP) gene has a 96-% sequence homology in comparison with ePNP and also has the ability to convert 6MePdR to 6MeP. In this study, we used tumor-targeting
S. typhimurium
VNP20009 expressing endogenous PNP gene constitutively to activate 6MePdR and a combination treatment of bacteria and prodrug in B16F10 melanoma model. The conversion of 6MePdR to 6MeP by
S. typhimurium
was analyzed by HPLC and the enzyme activity of sPNP was confirmed by in vitro (tetrazolium-based colorimetric assay) MTT cytotoxicity assay. After systemic administration of VNP20009 to mice, the bacteria largely accumulated and specifically delivered endogenous sPNP in the tumor. In comparison with VNP20009 or 6MePdR treatment alone, combined administration of VNP20009 followed by 6MePdR treatment significantly delayed the growth of B16F10 tumor and increased the CD8
+
T-cell infiltration. In summary, our results demonstrated that the combination therapy of
S. typhimurium
and prodrug 6MePdR is a promising strategy for cancer therapy.</description><identifier>ISSN: 0175-7598</identifier><identifier>EISSN: 1432-0614</identifier><identifier>DOI: 10.1007/s00253-012-4321-8</identifier><identifier>PMID: 22868826</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer-Verlag</publisher><subject>Amino Acid Sequence ; Analysis ; Animal models ; Animals ; Antineoplastic Agents - therapeutic use ; Apoptosis ; Bacteria ; Biomedical and Life Sciences ; Biotechnologically Relevant Enzymes and Proteins ; Biotechnology ; Cancer ; Cancer therapies ; Care and treatment ; Chromatography ; Chromatography, High Pressure Liquid ; Combination therapy ; Cytotoxicity ; E coli ; Enzymatic activity ; Enzymes ; Escherichia coli ; Female ; Gene expression ; Health aspects ; In Situ Nick-End Labeling ; Laboratories ; Laboratory animals ; Life Sciences ; Liquid chromatography ; Melanoma ; Melanoma, Experimental - drug therapy ; Melanoma, Experimental - pathology ; Melanoma, Experimental - therapy ; Mice ; Mice, Inbred C57BL ; Microbial Genetics and Genomics ; Microbiology ; Molecular Sequence Data ; Prodrugs - therapeutic use ; Purine Nucleosides - therapeutic use ; Purine-Nucleoside Phosphorylase - chemistry ; Salmonella ; Salmonella typhimurium ; Salmonella typhimurium - physiology ; Sequence Homology, Amino Acid ; Studies ; T cells ; Tumors</subject><ispartof>Applied microbiology and biotechnology, 2013-05, Vol.97 (10), p.4393-4401</ispartof><rights>Springer-Verlag 2012</rights><rights>COPYRIGHT 2013 Springer</rights><rights>Springer-Verlag 2013</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c543t-e1c2b36fa9d19ab997c38520022729bb9bcc9e20ba6b7e43c6b7dd61804ecfd53</citedby><cites>FETCH-LOGICAL-c543t-e1c2b36fa9d19ab997c38520022729bb9bcc9e20ba6b7e43c6b7dd61804ecfd53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00253-012-4321-8$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00253-012-4321-8$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22868826$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Guo</creatorcontrib><creatorcontrib>Tang, Bo</creatorcontrib><creatorcontrib>Yang, Bing-Ya</creatorcontrib><creatorcontrib>Chen, Jian-Xiang</creatorcontrib><creatorcontrib>Zhou, Jia-Hua</creatorcontrib><creatorcontrib>Li, Jia-Huang</creatorcontrib><creatorcontrib>Hua, Zi-Chun</creatorcontrib><title>Tumor-targeting Salmonella typhimurium, a natural tool for activation of prodrug 6MePdR and their combination therapy in murine melanoma model</title><title>Applied microbiology and biotechnology</title><addtitle>Appl Microbiol Biotechnol</addtitle><addtitle>Appl Microbiol Biotechnol</addtitle><description>The PNP/6-methylpurine 2′-deoxyriboside (6MePdR) system is an efficient gene-directed enzyme prodrug therapy system with significant antitumor activities. In this system,
Escherichia coli
purine nucleoside phosphorylase (ePNP) activates nontoxic 6MePdR into potent antitumor drug 6-methylpurine (6MeP). The
Salmonella typhimurium
PNP (sPNP) gene has a 96-% sequence homology in comparison with ePNP and also has the ability to convert 6MePdR to 6MeP. In this study, we used tumor-targeting
S. typhimurium
VNP20009 expressing endogenous PNP gene constitutively to activate 6MePdR and a combination treatment of bacteria and prodrug in B16F10 melanoma model. The conversion of 6MePdR to 6MeP by
S. typhimurium
was analyzed by HPLC and the enzyme activity of sPNP was confirmed by in vitro (tetrazolium-based colorimetric assay) MTT cytotoxicity assay. After systemic administration of VNP20009 to mice, the bacteria largely accumulated and specifically delivered endogenous sPNP in the tumor. In comparison with VNP20009 or 6MePdR treatment alone, combined administration of VNP20009 followed by 6MePdR treatment significantly delayed the growth of B16F10 tumor and increased the CD8
+
T-cell infiltration. In summary, our results demonstrated that the combination therapy of
S. typhimurium
and prodrug 6MePdR is a promising strategy for cancer therapy.</description><subject>Amino Acid Sequence</subject><subject>Analysis</subject><subject>Animal models</subject><subject>Animals</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Apoptosis</subject><subject>Bacteria</subject><subject>Biomedical and Life Sciences</subject><subject>Biotechnologically Relevant Enzymes and Proteins</subject><subject>Biotechnology</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Care and treatment</subject><subject>Chromatography</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Combination therapy</subject><subject>Cytotoxicity</subject><subject>E coli</subject><subject>Enzymatic activity</subject><subject>Enzymes</subject><subject>Escherichia coli</subject><subject>Female</subject><subject>Gene expression</subject><subject>Health aspects</subject><subject>In Situ Nick-End Labeling</subject><subject>Laboratories</subject><subject>Laboratory animals</subject><subject>Life Sciences</subject><subject>Liquid chromatography</subject><subject>Melanoma</subject><subject>Melanoma, Experimental - drug therapy</subject><subject>Melanoma, Experimental - pathology</subject><subject>Melanoma, Experimental - therapy</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Microbial Genetics and Genomics</subject><subject>Microbiology</subject><subject>Molecular Sequence Data</subject><subject>Prodrugs - therapeutic use</subject><subject>Purine Nucleosides - therapeutic use</subject><subject>Purine-Nucleoside Phosphorylase - chemistry</subject><subject>Salmonella</subject><subject>Salmonella typhimurium</subject><subject>Salmonella typhimurium - physiology</subject><subject>Sequence Homology, Amino Acid</subject><subject>Studies</subject><subject>T cells</subject><subject>Tumors</subject><issn>0175-7598</issn><issn>1432-0614</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqNkt1uFSEUhYnR2GP1AbwxJN7UxKn8zMBw2TRVm9Ro2npNGIaZ0gxwBMZ4XqLPLJOpP8doYrjYBL61sjcsAJ5jdIwR4m8SQqShFcKkqinBVfsAbHDZVYjh-iHYIMybijeiPQBPUrpFBWwZewwOSKltS9gG3F3PLsQqqziabP0Ir9TkgjfTpGDebW-sm6Od3WuooFd5jmqCOYQJDiFCpbP9qrINHoYBbmPo4zxC9sF86i-h8j3MN8ZGqIPrrF-5chLVdgeth4uxN9CZSfngFHShN9NT8GhQUzLP7ush-Pz27Pr0fXXx8d356clFpZua5spgTTrKBiV6LFQnBNe0bUh5DsKJ6DrRaS0MQZ1iHTc11aX0PcMtqo0e-oYegqPVt3T9ZTYpS2eTXqb2JsxJYtowQZHg7D_QWnCERb24vvwDvQ1z9GWQxZDjpm4E-0WNajLS-iHkqPRiKk8o5aVL0vBCHf-FKqs3zuryQ4Mt53uCV3uCwmTzLY9qTkmeX13us3hldQwpRTPIbbROxZ3ESC7Rkmu0ZEmMXKIl26J5cT_c3DnT_1T8yFIByAqkcuVHE3-b_p-u3wH3i9hV</recordid><startdate>20130501</startdate><enddate>20130501</enddate><creator>Chen, Guo</creator><creator>Tang, Bo</creator><creator>Yang, Bing-Ya</creator><creator>Chen, Jian-Xiang</creator><creator>Zhou, Jia-Hua</creator><creator>Li, Jia-Huang</creator><creator>Hua, Zi-Chun</creator><general>Springer-Verlag</general><general>Springer</general><general>Springer Nature B.V</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>ISR</scope><scope>3V.</scope><scope>7QL</scope><scope>7T7</scope><scope>7WY</scope><scope>7WZ</scope><scope>7X7</scope><scope>7XB</scope><scope>87Z</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8FL</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BEZIV</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FRNLG</scope><scope>FYUFA</scope><scope>F~G</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K60</scope><scope>K6~</scope><scope>K9.</scope><scope>L.-</scope><scope>LK8</scope><scope>M0C</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PQBIZ</scope><scope>PQBZA</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>7QO</scope></search><sort><creationdate>20130501</creationdate><title>Tumor-targeting Salmonella typhimurium, a natural tool for activation of prodrug 6MePdR and their combination therapy in murine melanoma model</title><author>Chen, Guo ; Tang, Bo ; Yang, Bing-Ya ; Chen, Jian-Xiang ; Zhou, Jia-Hua ; Li, Jia-Huang ; Hua, Zi-Chun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c543t-e1c2b36fa9d19ab997c38520022729bb9bcc9e20ba6b7e43c6b7dd61804ecfd53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Amino Acid Sequence</topic><topic>Analysis</topic><topic>Animal models</topic><topic>Animals</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Apoptosis</topic><topic>Bacteria</topic><topic>Biomedical and Life Sciences</topic><topic>Biotechnologically Relevant Enzymes and Proteins</topic><topic>Biotechnology</topic><topic>Cancer</topic><topic>Cancer therapies</topic><topic>Care and treatment</topic><topic>Chromatography</topic><topic>Chromatography, High Pressure Liquid</topic><topic>Combination therapy</topic><topic>Cytotoxicity</topic><topic>E coli</topic><topic>Enzymatic activity</topic><topic>Enzymes</topic><topic>Escherichia coli</topic><topic>Female</topic><topic>Gene expression</topic><topic>Health aspects</topic><topic>In Situ Nick-End Labeling</topic><topic>Laboratories</topic><topic>Laboratory animals</topic><topic>Life Sciences</topic><topic>Liquid chromatography</topic><topic>Melanoma</topic><topic>Melanoma, Experimental - drug therapy</topic><topic>Melanoma, Experimental - pathology</topic><topic>Melanoma, Experimental - therapy</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Microbial Genetics and Genomics</topic><topic>Microbiology</topic><topic>Molecular Sequence Data</topic><topic>Prodrugs - therapeutic use</topic><topic>Purine Nucleosides - therapeutic use</topic><topic>Purine-Nucleoside Phosphorylase - chemistry</topic><topic>Salmonella</topic><topic>Salmonella typhimurium</topic><topic>Salmonella typhimurium - physiology</topic><topic>Sequence Homology, Amino Acid</topic><topic>Studies</topic><topic>T cells</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Guo</creatorcontrib><creatorcontrib>Tang, Bo</creatorcontrib><creatorcontrib>Yang, Bing-Ya</creatorcontrib><creatorcontrib>Chen, Jian-Xiang</creatorcontrib><creatorcontrib>Zhou, Jia-Hua</creatorcontrib><creatorcontrib>Li, Jia-Huang</creatorcontrib><creatorcontrib>Hua, Zi-Chun</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Access via ABI/INFORM (ProQuest)</collection><collection>ABI/INFORM Global (PDF only)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ABI/INFORM Global (Alumni Edition)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</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>ABI/INFORM Collection (Alumni Edition)</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>Business Premium Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Business Premium Collection (Alumni)</collection><collection>Health Research Premium Collection</collection><collection>ABI/INFORM Global (Corporate)</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Business Collection (Alumni Edition)</collection><collection>ProQuest Business Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ABI/INFORM Professional Advanced</collection><collection>ProQuest Biological Science Collection</collection><collection>ABI/INFORM Global</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>One Business (ProQuest)</collection><collection>ProQuest One Business (Alumni)</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 Basic</collection><collection>MEDLINE - Academic</collection><collection>Biotechnology Research Abstracts</collection><jtitle>Applied microbiology and biotechnology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Guo</au><au>Tang, Bo</au><au>Yang, Bing-Ya</au><au>Chen, Jian-Xiang</au><au>Zhou, Jia-Hua</au><au>Li, Jia-Huang</au><au>Hua, Zi-Chun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tumor-targeting Salmonella typhimurium, a natural tool for activation of prodrug 6MePdR and their combination therapy in murine melanoma model</atitle><jtitle>Applied microbiology and biotechnology</jtitle><stitle>Appl Microbiol Biotechnol</stitle><addtitle>Appl Microbiol Biotechnol</addtitle><date>2013-05-01</date><risdate>2013</risdate><volume>97</volume><issue>10</issue><spage>4393</spage><epage>4401</epage><pages>4393-4401</pages><issn>0175-7598</issn><eissn>1432-0614</eissn><abstract>The PNP/6-methylpurine 2′-deoxyriboside (6MePdR) system is an efficient gene-directed enzyme prodrug therapy system with significant antitumor activities. In this system,
Escherichia coli
purine nucleoside phosphorylase (ePNP) activates nontoxic 6MePdR into potent antitumor drug 6-methylpurine (6MeP). The
Salmonella typhimurium
PNP (sPNP) gene has a 96-% sequence homology in comparison with ePNP and also has the ability to convert 6MePdR to 6MeP. In this study, we used tumor-targeting
S. typhimurium
VNP20009 expressing endogenous PNP gene constitutively to activate 6MePdR and a combination treatment of bacteria and prodrug in B16F10 melanoma model. The conversion of 6MePdR to 6MeP by
S. typhimurium
was analyzed by HPLC and the enzyme activity of sPNP was confirmed by in vitro (tetrazolium-based colorimetric assay) MTT cytotoxicity assay. After systemic administration of VNP20009 to mice, the bacteria largely accumulated and specifically delivered endogenous sPNP in the tumor. In comparison with VNP20009 or 6MePdR treatment alone, combined administration of VNP20009 followed by 6MePdR treatment significantly delayed the growth of B16F10 tumor and increased the CD8
+
T-cell infiltration. In summary, our results demonstrated that the combination therapy of
S. typhimurium
and prodrug 6MePdR is a promising strategy for cancer therapy.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer-Verlag</pub><pmid>22868826</pmid><doi>10.1007/s00253-012-4321-8</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0175-7598 |
| ispartof | Applied microbiology and biotechnology, 2013-05, Vol.97 (10), p.4393-4401 |
| issn | 0175-7598 1432-0614 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1356930976 |
| source | MEDLINE; SpringerNature Journals |
| subjects | Amino Acid Sequence Analysis Animal models Animals Antineoplastic Agents - therapeutic use Apoptosis Bacteria Biomedical and Life Sciences Biotechnologically Relevant Enzymes and Proteins Biotechnology Cancer Cancer therapies Care and treatment Chromatography Chromatography, High Pressure Liquid Combination therapy Cytotoxicity E coli Enzymatic activity Enzymes Escherichia coli Female Gene expression Health aspects In Situ Nick-End Labeling Laboratories Laboratory animals Life Sciences Liquid chromatography Melanoma Melanoma, Experimental - drug therapy Melanoma, Experimental - pathology Melanoma, Experimental - therapy Mice Mice, Inbred C57BL Microbial Genetics and Genomics Microbiology Molecular Sequence Data Prodrugs - therapeutic use Purine Nucleosides - therapeutic use Purine-Nucleoside Phosphorylase - chemistry Salmonella Salmonella typhimurium Salmonella typhimurium - physiology Sequence Homology, Amino Acid Studies T cells Tumors |
| title | Tumor-targeting Salmonella typhimurium, a natural tool for activation of prodrug 6MePdR and their combination therapy in murine melanoma model |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T02%3A02%3A37IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Tumor-targeting%20Salmonella%20typhimurium,%20a%20natural%20tool%20for%20activation%20of%20prodrug%206MePdR%20and%20their%20combination%20therapy%20in%20murine%20melanoma%20model&rft.jtitle=Applied%20microbiology%20and%20biotechnology&rft.au=Chen,%20Guo&rft.date=2013-05-01&rft.volume=97&rft.issue=10&rft.spage=4393&rft.epage=4401&rft.pages=4393-4401&rft.issn=0175-7598&rft.eissn=1432-0614&rft_id=info:doi/10.1007/s00253-012-4321-8&rft_dat=%3Cgale_proqu%3EA337618257%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1357154596&rft_id=info:pmid/22868826&rft_galeid=A337618257&rfr_iscdi=true |