S- and G2-phase Cell Cycle Arrests and Apoptosis Induced by Ganciclovir in Murine Melanoma Cells Transduced with Herpes Simplex Virus Thymidine Kinase
Mechanism of cell killing by transfer of Herpes simplex virus type-1 thymidine kinase (HSVtk) and subsequent ganciclovir (GCV) treatment was examined in B16F10 murine melanoma model. While parental B16F10 melanoma cells were resistant to GCV at 100 μM or higher,HSVtk-transduced B16F10 melanoma cell...
Gespeichert in:
| Veröffentlicht in: | Experimental cell research 1998-05, Vol.241 (1), p.66-75 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 75 |
|---|---|
| container_issue | 1 |
| container_start_page | 66 |
| container_title | Experimental cell research |
| container_volume | 241 |
| creator | Wei, Sung-Jen Chao, Yee Hung, Yi-Mei Lin, Wen-chang Yang, Den-Mei Shih, Yung-Luen Ch'ang, Lan-Yang Whang-Peng, Jacqueline Yang, Wen K |
| description | Mechanism of cell killing by transfer of Herpes simplex virus type-1 thymidine kinase (HSVtk) and subsequent ganciclovir (GCV) treatment was examined in B16F10 murine melanoma model. While parental B16F10 melanoma cells were resistant to GCV at 100 μM or higher,HSVtk-transduced B16F10 melanoma cell clones became susceptible to GCV with IC50of 0.1 to 0.3 μM. By means of various parameters including characteristic morphological changes,in situDNA end-labeling, DNA ladder pattern, flow cytometric detection of sub-G1 DNA content, and annexin V binding of inverted cell surface phosphatidylserine, apoptosis was shown to be associated with the cell killing of ganciclovir onHSVtk-transduced melanoma B16F10 cells. Kinetic analysis showed that the signs of apoptosis were observed not until 60 h of continued GCV treatment and preceded first by a rise in p53 protein level in 12 h and then by S-phase/G2-phase cell cycle arrest associated with corresponding increases in the level of cyclin B1 protein but no apparent change in protein level of Bax or Cdc2. These results suggest that apoptosis occurred as a result of ganciclovir-induced cell cycle arrests rather than direct chemical effect onHSVtk-transduced B16F10 melanoma cells. |
| doi_str_mv | 10.1006/excr.1998.4005 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_79946276</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0014482798940058</els_id><sourcerecordid>79946276</sourcerecordid><originalsourceid>FETCH-LOGICAL-c339t-5eae53b37977a09bf5188404f68e86ea2590758588e02c4aedf28d37cd731d6e3</originalsourceid><addsrcrecordid>eNp1Uctu1DAUtRCoTAtbdkhescvgV2J7ORrBtGorFi1sLY99ozFKnGAnpfMjfC9OZ8SO1V2ch849B6EPlKwpIc1neHZpTbVWa0FI_QqtKNGkYoKx12hFCBWVUEy-RZc5_ySEKEWbC3ShG85rKlboz0OFbfR4x6rxYDPgLXQd3h5dB3iTEuQpv-CbcRinIYeMb6KfHXi8P-KdjS64bngKCYeI7-cUIuB76GwcevtilfFjsjGfJL_DdMDXkEbI-CH0YwfP-EdIcyEdjn3wi_o2xBLjHXrT2i7D-_O9Qt-_fnncXld333Y3281d5TjXU1WDhZrvudRSWqL3bU2VEkS0jQLVgGW1JrJWtVJAmBMWfMuU59J5yalvgF-hTyffMQ2_5vKt6UN2JbeNMMzZSK1Fw2RTiOsT0aUh5wStGVPobToaSswyhFmGMMsQZhmiCD6ened9D_4f_dx8wdUJh_LeU4BksgsQS00hgZuMH8L_rP8CeGeYdQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>79946276</pqid></control><display><type>article</type><title>S- and G2-phase Cell Cycle Arrests and Apoptosis Induced by Ganciclovir in Murine Melanoma Cells Transduced with Herpes Simplex Virus Thymidine Kinase</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Wei, Sung-Jen ; Chao, Yee ; Hung, Yi-Mei ; Lin, Wen-chang ; Yang, Den-Mei ; Shih, Yung-Luen ; Ch'ang, Lan-Yang ; Whang-Peng, Jacqueline ; Yang, Wen K</creator><creatorcontrib>Wei, Sung-Jen ; Chao, Yee ; Hung, Yi-Mei ; Lin, Wen-chang ; Yang, Den-Mei ; Shih, Yung-Luen ; Ch'ang, Lan-Yang ; Whang-Peng, Jacqueline ; Yang, Wen K</creatorcontrib><description>Mechanism of cell killing by transfer of Herpes simplex virus type-1 thymidine kinase (HSVtk) and subsequent ganciclovir (GCV) treatment was examined in B16F10 murine melanoma model. While parental B16F10 melanoma cells were resistant to GCV at 100 μM or higher,HSVtk-transduced B16F10 melanoma cell clones became susceptible to GCV with IC50of 0.1 to 0.3 μM. By means of various parameters including characteristic morphological changes,in situDNA end-labeling, DNA ladder pattern, flow cytometric detection of sub-G1 DNA content, and annexin V binding of inverted cell surface phosphatidylserine, apoptosis was shown to be associated with the cell killing of ganciclovir onHSVtk-transduced melanoma B16F10 cells. Kinetic analysis showed that the signs of apoptosis were observed not until 60 h of continued GCV treatment and preceded first by a rise in p53 protein level in 12 h and then by S-phase/G2-phase cell cycle arrest associated with corresponding increases in the level of cyclin B1 protein but no apparent change in protein level of Bax or Cdc2. These results suggest that apoptosis occurred as a result of ganciclovir-induced cell cycle arrests rather than direct chemical effect onHSVtk-transduced B16F10 melanoma cells.</description><identifier>ISSN: 0014-4827</identifier><identifier>EISSN: 1090-2422</identifier><identifier>DOI: 10.1006/excr.1998.4005</identifier><identifier>PMID: 9633514</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Antiviral Agents - administration & dosage ; Antiviral Agents - therapeutic use ; apoptosis ; Apoptosis - drug effects ; Apoptosis - physiology ; bystander effect ; cell cycle ; Cell Cycle - drug effects ; Cell Cycle Proteins - drug effects ; Cell Transplantation ; Cyclin B - metabolism ; Disease Models, Animal ; DNA Fragmentation - drug effects ; DNA Fragmentation - genetics ; Female ; G2 Phase - drug effects ; Ganciclovir - administration & dosage ; Ganciclovir - therapeutic use ; GCV ; Gene Transfer Techniques ; Genetic Therapy - methods ; Genetic Vectors ; HSVtk ; Kinetics ; melanoma cells ; Melanoma, Experimental - chemistry ; Melanoma, Experimental - pathology ; Melanoma, Experimental - therapy ; Membrane Lipids - metabolism ; Mice ; Mice, Inbred C57BL ; Neoplasm Transplantation ; Phosphatidylserines - metabolism ; Recombinant Fusion Proteins - genetics ; S Phase - drug effects ; Simplexvirus - enzymology ; Thymidine Kinase - genetics ; Transfection - genetics ; Tumor Cells, Cultured - drug effects ; Tumor Cells, Cultured - physiology ; Tumor Suppressor Protein p53 - metabolism</subject><ispartof>Experimental cell research, 1998-05, Vol.241 (1), p.66-75</ispartof><rights>1998 Academic Press</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c339t-5eae53b37977a09bf5188404f68e86ea2590758588e02c4aedf28d37cd731d6e3</citedby><cites>FETCH-LOGICAL-c339t-5eae53b37977a09bf5188404f68e86ea2590758588e02c4aedf28d37cd731d6e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1006/excr.1998.4005$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9633514$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wei, Sung-Jen</creatorcontrib><creatorcontrib>Chao, Yee</creatorcontrib><creatorcontrib>Hung, Yi-Mei</creatorcontrib><creatorcontrib>Lin, Wen-chang</creatorcontrib><creatorcontrib>Yang, Den-Mei</creatorcontrib><creatorcontrib>Shih, Yung-Luen</creatorcontrib><creatorcontrib>Ch'ang, Lan-Yang</creatorcontrib><creatorcontrib>Whang-Peng, Jacqueline</creatorcontrib><creatorcontrib>Yang, Wen K</creatorcontrib><title>S- and G2-phase Cell Cycle Arrests and Apoptosis Induced by Ganciclovir in Murine Melanoma Cells Transduced with Herpes Simplex Virus Thymidine Kinase</title><title>Experimental cell research</title><addtitle>Exp Cell Res</addtitle><description>Mechanism of cell killing by transfer of Herpes simplex virus type-1 thymidine kinase (HSVtk) and subsequent ganciclovir (GCV) treatment was examined in B16F10 murine melanoma model. While parental B16F10 melanoma cells were resistant to GCV at 100 μM or higher,HSVtk-transduced B16F10 melanoma cell clones became susceptible to GCV with IC50of 0.1 to 0.3 μM. By means of various parameters including characteristic morphological changes,in situDNA end-labeling, DNA ladder pattern, flow cytometric detection of sub-G1 DNA content, and annexin V binding of inverted cell surface phosphatidylserine, apoptosis was shown to be associated with the cell killing of ganciclovir onHSVtk-transduced melanoma B16F10 cells. Kinetic analysis showed that the signs of apoptosis were observed not until 60 h of continued GCV treatment and preceded first by a rise in p53 protein level in 12 h and then by S-phase/G2-phase cell cycle arrest associated with corresponding increases in the level of cyclin B1 protein but no apparent change in protein level of Bax or Cdc2. These results suggest that apoptosis occurred as a result of ganciclovir-induced cell cycle arrests rather than direct chemical effect onHSVtk-transduced B16F10 melanoma cells.</description><subject>Animals</subject><subject>Antiviral Agents - administration & dosage</subject><subject>Antiviral Agents - therapeutic use</subject><subject>apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Apoptosis - physiology</subject><subject>bystander effect</subject><subject>cell cycle</subject><subject>Cell Cycle - drug effects</subject><subject>Cell Cycle Proteins - drug effects</subject><subject>Cell Transplantation</subject><subject>Cyclin B - metabolism</subject><subject>Disease Models, Animal</subject><subject>DNA Fragmentation - drug effects</subject><subject>DNA Fragmentation - genetics</subject><subject>Female</subject><subject>G2 Phase - drug effects</subject><subject>Ganciclovir - administration & dosage</subject><subject>Ganciclovir - therapeutic use</subject><subject>GCV</subject><subject>Gene Transfer Techniques</subject><subject>Genetic Therapy - methods</subject><subject>Genetic Vectors</subject><subject>HSVtk</subject><subject>Kinetics</subject><subject>melanoma cells</subject><subject>Melanoma, Experimental - chemistry</subject><subject>Melanoma, Experimental - pathology</subject><subject>Melanoma, Experimental - therapy</subject><subject>Membrane Lipids - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Neoplasm Transplantation</subject><subject>Phosphatidylserines - metabolism</subject><subject>Recombinant Fusion Proteins - genetics</subject><subject>S Phase - drug effects</subject><subject>Simplexvirus - enzymology</subject><subject>Thymidine Kinase - genetics</subject><subject>Transfection - genetics</subject><subject>Tumor Cells, Cultured - drug effects</subject><subject>Tumor Cells, Cultured - physiology</subject><subject>Tumor Suppressor Protein p53 - metabolism</subject><issn>0014-4827</issn><issn>1090-2422</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1Uctu1DAUtRCoTAtbdkhescvgV2J7ORrBtGorFi1sLY99ozFKnGAnpfMjfC9OZ8SO1V2ch849B6EPlKwpIc1neHZpTbVWa0FI_QqtKNGkYoKx12hFCBWVUEy-RZc5_ySEKEWbC3ShG85rKlboz0OFbfR4x6rxYDPgLXQd3h5dB3iTEuQpv-CbcRinIYeMb6KfHXi8P-KdjS64bngKCYeI7-cUIuB76GwcevtilfFjsjGfJL_DdMDXkEbI-CH0YwfP-EdIcyEdjn3wi_o2xBLjHXrT2i7D-_O9Qt-_fnncXld333Y3281d5TjXU1WDhZrvudRSWqL3bU2VEkS0jQLVgGW1JrJWtVJAmBMWfMuU59J5yalvgF-hTyffMQ2_5vKt6UN2JbeNMMzZSK1Fw2RTiOsT0aUh5wStGVPobToaSswyhFmGMMsQZhmiCD6ened9D_4f_dx8wdUJh_LeU4BksgsQS00hgZuMH8L_rP8CeGeYdQ</recordid><startdate>19980525</startdate><enddate>19980525</enddate><creator>Wei, Sung-Jen</creator><creator>Chao, Yee</creator><creator>Hung, Yi-Mei</creator><creator>Lin, Wen-chang</creator><creator>Yang, Den-Mei</creator><creator>Shih, Yung-Luen</creator><creator>Ch'ang, Lan-Yang</creator><creator>Whang-Peng, Jacqueline</creator><creator>Yang, Wen K</creator><general>Elsevier Inc</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>19980525</creationdate><title>S- and G2-phase Cell Cycle Arrests and Apoptosis Induced by Ganciclovir in Murine Melanoma Cells Transduced with Herpes Simplex Virus Thymidine Kinase</title><author>Wei, Sung-Jen ; Chao, Yee ; Hung, Yi-Mei ; Lin, Wen-chang ; Yang, Den-Mei ; Shih, Yung-Luen ; Ch'ang, Lan-Yang ; Whang-Peng, Jacqueline ; Yang, Wen K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c339t-5eae53b37977a09bf5188404f68e86ea2590758588e02c4aedf28d37cd731d6e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Animals</topic><topic>Antiviral Agents - administration & dosage</topic><topic>Antiviral Agents - therapeutic use</topic><topic>apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Apoptosis - physiology</topic><topic>bystander effect</topic><topic>cell cycle</topic><topic>Cell Cycle - drug effects</topic><topic>Cell Cycle Proteins - drug effects</topic><topic>Cell Transplantation</topic><topic>Cyclin B - metabolism</topic><topic>Disease Models, Animal</topic><topic>DNA Fragmentation - drug effects</topic><topic>DNA Fragmentation - genetics</topic><topic>Female</topic><topic>G2 Phase - drug effects</topic><topic>Ganciclovir - administration & dosage</topic><topic>Ganciclovir - therapeutic use</topic><topic>GCV</topic><topic>Gene Transfer Techniques</topic><topic>Genetic Therapy - methods</topic><topic>Genetic Vectors</topic><topic>HSVtk</topic><topic>Kinetics</topic><topic>melanoma cells</topic><topic>Melanoma, Experimental - chemistry</topic><topic>Melanoma, Experimental - pathology</topic><topic>Melanoma, Experimental - therapy</topic><topic>Membrane Lipids - metabolism</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Neoplasm Transplantation</topic><topic>Phosphatidylserines - metabolism</topic><topic>Recombinant Fusion Proteins - genetics</topic><topic>S Phase - drug effects</topic><topic>Simplexvirus - enzymology</topic><topic>Thymidine Kinase - genetics</topic><topic>Transfection - genetics</topic><topic>Tumor Cells, Cultured - drug effects</topic><topic>Tumor Cells, Cultured - physiology</topic><topic>Tumor Suppressor Protein p53 - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wei, Sung-Jen</creatorcontrib><creatorcontrib>Chao, Yee</creatorcontrib><creatorcontrib>Hung, Yi-Mei</creatorcontrib><creatorcontrib>Lin, Wen-chang</creatorcontrib><creatorcontrib>Yang, Den-Mei</creatorcontrib><creatorcontrib>Shih, Yung-Luen</creatorcontrib><creatorcontrib>Ch'ang, Lan-Yang</creatorcontrib><creatorcontrib>Whang-Peng, Jacqueline</creatorcontrib><creatorcontrib>Yang, Wen K</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>Experimental cell research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wei, Sung-Jen</au><au>Chao, Yee</au><au>Hung, Yi-Mei</au><au>Lin, Wen-chang</au><au>Yang, Den-Mei</au><au>Shih, Yung-Luen</au><au>Ch'ang, Lan-Yang</au><au>Whang-Peng, Jacqueline</au><au>Yang, Wen K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>S- and G2-phase Cell Cycle Arrests and Apoptosis Induced by Ganciclovir in Murine Melanoma Cells Transduced with Herpes Simplex Virus Thymidine Kinase</atitle><jtitle>Experimental cell research</jtitle><addtitle>Exp Cell Res</addtitle><date>1998-05-25</date><risdate>1998</risdate><volume>241</volume><issue>1</issue><spage>66</spage><epage>75</epage><pages>66-75</pages><issn>0014-4827</issn><eissn>1090-2422</eissn><abstract>Mechanism of cell killing by transfer of Herpes simplex virus type-1 thymidine kinase (HSVtk) and subsequent ganciclovir (GCV) treatment was examined in B16F10 murine melanoma model. While parental B16F10 melanoma cells were resistant to GCV at 100 μM or higher,HSVtk-transduced B16F10 melanoma cell clones became susceptible to GCV with IC50of 0.1 to 0.3 μM. By means of various parameters including characteristic morphological changes,in situDNA end-labeling, DNA ladder pattern, flow cytometric detection of sub-G1 DNA content, and annexin V binding of inverted cell surface phosphatidylserine, apoptosis was shown to be associated with the cell killing of ganciclovir onHSVtk-transduced melanoma B16F10 cells. Kinetic analysis showed that the signs of apoptosis were observed not until 60 h of continued GCV treatment and preceded first by a rise in p53 protein level in 12 h and then by S-phase/G2-phase cell cycle arrest associated with corresponding increases in the level of cyclin B1 protein but no apparent change in protein level of Bax or Cdc2. These results suggest that apoptosis occurred as a result of ganciclovir-induced cell cycle arrests rather than direct chemical effect onHSVtk-transduced B16F10 melanoma cells.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>9633514</pmid><doi>10.1006/excr.1998.4005</doi><tpages>10</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0014-4827 |
| ispartof | Experimental cell research, 1998-05, Vol.241 (1), p.66-75 |
| issn | 0014-4827 1090-2422 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_79946276 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Animals Antiviral Agents - administration & dosage Antiviral Agents - therapeutic use apoptosis Apoptosis - drug effects Apoptosis - physiology bystander effect cell cycle Cell Cycle - drug effects Cell Cycle Proteins - drug effects Cell Transplantation Cyclin B - metabolism Disease Models, Animal DNA Fragmentation - drug effects DNA Fragmentation - genetics Female G2 Phase - drug effects Ganciclovir - administration & dosage Ganciclovir - therapeutic use GCV Gene Transfer Techniques Genetic Therapy - methods Genetic Vectors HSVtk Kinetics melanoma cells Melanoma, Experimental - chemistry Melanoma, Experimental - pathology Melanoma, Experimental - therapy Membrane Lipids - metabolism Mice Mice, Inbred C57BL Neoplasm Transplantation Phosphatidylserines - metabolism Recombinant Fusion Proteins - genetics S Phase - drug effects Simplexvirus - enzymology Thymidine Kinase - genetics Transfection - genetics Tumor Cells, Cultured - drug effects Tumor Cells, Cultured - physiology Tumor Suppressor Protein p53 - metabolism |
| title | S- and G2-phase Cell Cycle Arrests and Apoptosis Induced by Ganciclovir in Murine Melanoma Cells Transduced with Herpes Simplex Virus Thymidine Kinase |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-18T00%3A35%3A48IST&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=S-%20and%20G2-phase%20Cell%20Cycle%20Arrests%20and%20Apoptosis%20Induced%20by%20Ganciclovir%20in%20Murine%20Melanoma%20Cells%20Transduced%20with%20Herpes%20Simplex%20Virus%20Thymidine%20Kinase&rft.jtitle=Experimental%20cell%20research&rft.au=Wei,%20Sung-Jen&rft.date=1998-05-25&rft.volume=241&rft.issue=1&rft.spage=66&rft.epage=75&rft.pages=66-75&rft.issn=0014-4827&rft.eissn=1090-2422&rft_id=info:doi/10.1006/excr.1998.4005&rft_dat=%3Cproquest_cross%3E79946276%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=79946276&rft_id=info:pmid/9633514&rft_els_id=S0014482798940058&rfr_iscdi=true |