Antitumor activity of benzamide riboside and its combination with cisplatin and staurosporine
Benzamide riboside (BR), a new synthetic nucleoside analogue, has demonstrated a potent cytotoxic activity in murine leukemia in vitro. The purpose of the present investigation was to examine the antitumor activity of BR in mice bearing leukemia L1210. The results revealed that BR possesses a potent...
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Veröffentlicht in: | European journal of pharmaceutical sciences 2001-02, Vol.12 (4), p.387-394 |
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description | Benzamide riboside (BR), a new synthetic nucleoside analogue, has demonstrated a potent cytotoxic activity in murine leukemia in vitro. The purpose of the present investigation was to examine the antitumor activity of BR in mice bearing leukemia L1210. The results revealed that BR possesses a potent antitumor activity in vivo. It increases life-span of mice with leukemia. Synergistic cytotoxicity of BR with select DNA damaging agents, cisplatin (cis-Pt) and staurosporine (STP) was examined in MTT chemosensitivity assay, FACS analyses and apoptotic DNA fragmentation on L1210 cells in culture. A simultaneous treatment of leukemia L1210 cells with the combination of BR and STP resulted in synergistic cytotoxicity that correlated with increased apoptotic activity in those cells. On the other hand, treatment of L1210 cells with combination of BR and cis-Pt resulted in antagonistic cytotoxic effect. Finally, to elucidate the synergistic effect of BR and STP in inducing apoptosis, the attention was directed to the activation of cell death processes through various cell cycle signals. This is the first report describing in vivo antitumor activity of BR and its utilization in combination chemotherapy. |
doi_str_mv | 10.1016/S0928-0987(00)00180-9 |
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The purpose of the present investigation was to examine the antitumor activity of BR in mice bearing leukemia L1210. The results revealed that BR possesses a potent antitumor activity in vivo. It increases life-span of mice with leukemia. Synergistic cytotoxicity of BR with select DNA damaging agents, cisplatin (cis-Pt) and staurosporine (STP) was examined in MTT chemosensitivity assay, FACS analyses and apoptotic DNA fragmentation on L1210 cells in culture. A simultaneous treatment of leukemia L1210 cells with the combination of BR and STP resulted in synergistic cytotoxicity that correlated with increased apoptotic activity in those cells. On the other hand, treatment of L1210 cells with combination of BR and cis-Pt resulted in antagonistic cytotoxic effect. Finally, to elucidate the synergistic effect of BR and STP in inducing apoptosis, the attention was directed to the activation of cell death processes through various cell cycle signals. This is the first report describing in vivo antitumor activity of BR and its utilization in combination chemotherapy.</description><identifier>ISSN: 0928-0987</identifier><identifier>EISSN: 1879-0720</identifier><identifier>DOI: 10.1016/S0928-0987(00)00180-9</identifier><identifier>PMID: 11231105</identifier><language>eng</language><publisher>Shannon: Elsevier B.V</publisher><subject>Animals ; Antineoplastic agents ; Antineoplastic Agents - therapeutic use ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Apoptosis ; Apoptosis - drug effects ; Apoptosis - physiology ; Benzamide riboside ; Biological and medical sciences ; Cisplatin ; Cisplatin - administration & dosage ; Cytotoxicity ; Drug Screening Assays, Antitumor ; Enzyme Inhibitors - administration & dosage ; General aspects ; Leukemia L1210 - drug therapy ; Leukemia L1210 - mortality ; Medical sciences ; Mice ; Mice, Inbred DBA ; Murine leukemia cells ; Nucleosides - administration & dosage ; Pharmacology. Drug treatments ; Staurosporine ; Staurosporine - administration & dosage ; Survival Rate</subject><ispartof>European journal of pharmaceutical sciences, 2001-02, Vol.12 (4), p.387-394</ispartof><rights>2001 Elsevier Science B.V.</rights><rights>2001 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c389t-60ce11cbee1c529da92405d5c05334b0d9d705f0f97e78ec1d3ffabdabf959063</citedby><cites>FETCH-LOGICAL-c389t-60ce11cbee1c529da92405d5c05334b0d9d705f0f97e78ec1d3ffabdabf959063</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0928-0987(00)00180-9$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=912686$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11231105$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rauko, Peter</creatorcontrib><creatorcontrib>Novotny, Ladislav</creatorcontrib><creatorcontrib>Dovinova, Ima</creatorcontrib><creatorcontrib>Hunakova, Luba</creatorcontrib><creatorcontrib>Szekeres, Thomas</creatorcontrib><creatorcontrib>Jayaram, Hiremagalur N.</creatorcontrib><title>Antitumor activity of benzamide riboside and its combination with cisplatin and staurosporine</title><title>European journal of pharmaceutical sciences</title><addtitle>Eur J Pharm Sci</addtitle><description>Benzamide riboside (BR), a new synthetic nucleoside analogue, has demonstrated a potent cytotoxic activity in murine leukemia in vitro. The purpose of the present investigation was to examine the antitumor activity of BR in mice bearing leukemia L1210. The results revealed that BR possesses a potent antitumor activity in vivo. It increases life-span of mice with leukemia. Synergistic cytotoxicity of BR with select DNA damaging agents, cisplatin (cis-Pt) and staurosporine (STP) was examined in MTT chemosensitivity assay, FACS analyses and apoptotic DNA fragmentation on L1210 cells in culture. A simultaneous treatment of leukemia L1210 cells with the combination of BR and STP resulted in synergistic cytotoxicity that correlated with increased apoptotic activity in those cells. On the other hand, treatment of L1210 cells with combination of BR and cis-Pt resulted in antagonistic cytotoxic effect. Finally, to elucidate the synergistic effect of BR and STP in inducing apoptosis, the attention was directed to the activation of cell death processes through various cell cycle signals. This is the first report describing in vivo antitumor activity of BR and its utilization in combination chemotherapy.</description><subject>Animals</subject><subject>Antineoplastic agents</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Apoptosis - physiology</subject><subject>Benzamide riboside</subject><subject>Biological and medical sciences</subject><subject>Cisplatin</subject><subject>Cisplatin - administration & dosage</subject><subject>Cytotoxicity</subject><subject>Drug Screening Assays, Antitumor</subject><subject>Enzyme Inhibitors - administration & dosage</subject><subject>General aspects</subject><subject>Leukemia L1210 - drug therapy</subject><subject>Leukemia L1210 - mortality</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred DBA</subject><subject>Murine leukemia cells</subject><subject>Nucleosides - administration & dosage</subject><subject>Pharmacology. Drug treatments</subject><subject>Staurosporine</subject><subject>Staurosporine - administration & dosage</subject><subject>Survival Rate</subject><issn>0928-0987</issn><issn>1879-0720</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE9rFjEQh0OxtK_Vj6AsCGIPWye7zW5yKqVoWyj0oB4lZJMJjuwmr0m2pX569_1DPfY0M_DMzI-HsXcczjjw7vM3UI2sQcn-E8ApAJdQqwO24rJXNfQNvGKrZ-SYvc75NwB0socjdsx503IOYsV-XoZCZZ5iqowt9EDlqYq-GjD8NRM5rBINMW8aE1xFJVc2TgMFUyiG6pHKr8pSXo_LHLZILmZOMa9jooBv2KE3Y8a3-3rCfnz98v3qpr67v769uryrbStVqTuwyLkdELkVjXJGNecgnLAg2vZ8AKdcD8KDVz32Ei13rfdmcGbwSijo2hP2cXd3neKfGXPRE2WL42gCxjnrvlNStNAsoNiBdsmYE3q9TjSZ9KQ56I1XvfWqN9I0gN561WrZe79_MA8Tuv9be5EL8GEPmGzN6JMJi5dnTvGmk5ucFzsKFxkPhElnSxgsOkpoi3aRXgjyDz-Ilk8</recordid><startdate>20010201</startdate><enddate>20010201</enddate><creator>Rauko, Peter</creator><creator>Novotny, Ladislav</creator><creator>Dovinova, Ima</creator><creator>Hunakova, Luba</creator><creator>Szekeres, Thomas</creator><creator>Jayaram, Hiremagalur N.</creator><general>Elsevier B.V</general><general>Elsevier</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>7X8</scope></search><sort><creationdate>20010201</creationdate><title>Antitumor activity of benzamide riboside and its combination with cisplatin and staurosporine</title><author>Rauko, Peter ; Novotny, Ladislav ; Dovinova, Ima ; Hunakova, Luba ; Szekeres, Thomas ; Jayaram, Hiremagalur N.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c389t-60ce11cbee1c529da92405d5c05334b0d9d705f0f97e78ec1d3ffabdabf959063</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Animals</topic><topic>Antineoplastic agents</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Apoptosis - physiology</topic><topic>Benzamide riboside</topic><topic>Biological and medical sciences</topic><topic>Cisplatin</topic><topic>Cisplatin - administration & dosage</topic><topic>Cytotoxicity</topic><topic>Drug Screening Assays, Antitumor</topic><topic>Enzyme Inhibitors - administration & dosage</topic><topic>General aspects</topic><topic>Leukemia L1210 - drug therapy</topic><topic>Leukemia L1210 - mortality</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred DBA</topic><topic>Murine leukemia cells</topic><topic>Nucleosides - administration & dosage</topic><topic>Pharmacology. Drug treatments</topic><topic>Staurosporine</topic><topic>Staurosporine - administration & dosage</topic><topic>Survival Rate</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rauko, Peter</creatorcontrib><creatorcontrib>Novotny, Ladislav</creatorcontrib><creatorcontrib>Dovinova, Ima</creatorcontrib><creatorcontrib>Hunakova, Luba</creatorcontrib><creatorcontrib>Szekeres, Thomas</creatorcontrib><creatorcontrib>Jayaram, Hiremagalur N.</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>MEDLINE - Academic</collection><jtitle>European journal of pharmaceutical sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rauko, Peter</au><au>Novotny, Ladislav</au><au>Dovinova, Ima</au><au>Hunakova, Luba</au><au>Szekeres, Thomas</au><au>Jayaram, Hiremagalur N.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antitumor activity of benzamide riboside and its combination with cisplatin and staurosporine</atitle><jtitle>European journal of pharmaceutical sciences</jtitle><addtitle>Eur J Pharm Sci</addtitle><date>2001-02-01</date><risdate>2001</risdate><volume>12</volume><issue>4</issue><spage>387</spage><epage>394</epage><pages>387-394</pages><issn>0928-0987</issn><eissn>1879-0720</eissn><abstract>Benzamide riboside (BR), a new synthetic nucleoside analogue, has demonstrated a potent cytotoxic activity in murine leukemia in vitro. The purpose of the present investigation was to examine the antitumor activity of BR in mice bearing leukemia L1210. The results revealed that BR possesses a potent antitumor activity in vivo. It increases life-span of mice with leukemia. Synergistic cytotoxicity of BR with select DNA damaging agents, cisplatin (cis-Pt) and staurosporine (STP) was examined in MTT chemosensitivity assay, FACS analyses and apoptotic DNA fragmentation on L1210 cells in culture. A simultaneous treatment of leukemia L1210 cells with the combination of BR and STP resulted in synergistic cytotoxicity that correlated with increased apoptotic activity in those cells. On the other hand, treatment of L1210 cells with combination of BR and cis-Pt resulted in antagonistic cytotoxic effect. Finally, to elucidate the synergistic effect of BR and STP in inducing apoptosis, the attention was directed to the activation of cell death processes through various cell cycle signals. This is the first report describing in vivo antitumor activity of BR and its utilization in combination chemotherapy.</abstract><cop>Shannon</cop><pub>Elsevier B.V</pub><pmid>11231105</pmid><doi>10.1016/S0928-0987(00)00180-9</doi><tpages>8</tpages></addata></record> |
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subjects | Animals Antineoplastic agents Antineoplastic Agents - therapeutic use Antineoplastic Combined Chemotherapy Protocols - therapeutic use Apoptosis Apoptosis - drug effects Apoptosis - physiology Benzamide riboside Biological and medical sciences Cisplatin Cisplatin - administration & dosage Cytotoxicity Drug Screening Assays, Antitumor Enzyme Inhibitors - administration & dosage General aspects Leukemia L1210 - drug therapy Leukemia L1210 - mortality Medical sciences Mice Mice, Inbred DBA Murine leukemia cells Nucleosides - administration & dosage Pharmacology. Drug treatments Staurosporine Staurosporine - administration & dosage Survival Rate |
title | Antitumor activity of benzamide riboside and its combination with cisplatin and staurosporine |
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