Enhancement of methotrexate cytotoxicity towards the MDA.MB.436 human breast cancer cell line by dipyridamole: The role of methotrexate polyglutamates
MTX and dipyridamole are synergistic in their toxicity towards the MDA.MB.436 human breast cancer cell line. Dipyridamole increases net MTX uptake into the cells and increases the intracellular levels of MTXG7 to G10, the highest molecular weight polyglutamyl derivatives of MTX detected. During a re...
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Veröffentlicht in: | Biochemical pharmacology 1986-09, Vol.35 (18), p.3053-3056 |
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creator | Kennedy, D.G. Van den Berg, H.W. Clarke, R. Murphy, R.F. |
description | MTX and dipyridamole are synergistic in their toxicity towards the MDA.MB.436 human breast cancer cell line. Dipyridamole increases net MTX uptake into the cells and increases the intracellular levels of MTXG7 to G10, the highest molecular weight polyglutamyl derivatives of MTX detected. During a recovery period, after completion of exposure to MTX with and without dipyridamole, levels of MTXG7 to G10 remained elevated in dipyridamole treated cells by comparison with controls. Dipyridamole, which has no intrinsic effect on cell growth, transforms a cytostatic response of MDA.MB.436 cells towards MTX into a cytotoxic response. The effect of dipyridamole is not mediated through an increase in prostacyclin biosynthesis. |
doi_str_mv | 10.1016/0006-2952(86)90385-0 |
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Dipyridamole increases net MTX uptake into the cells and increases the intracellular levels of MTXG7 to G10, the highest molecular weight polyglutamyl derivatives of MTX detected. During a recovery period, after completion of exposure to MTX with and without dipyridamole, levels of MTXG7 to G10 remained elevated in dipyridamole treated cells by comparison with controls. Dipyridamole, which has no intrinsic effect on cell growth, transforms a cytostatic response of MDA.MB.436 cells towards MTX into a cytotoxic response. The effect of dipyridamole is not mediated through an increase in prostacyclin biosynthesis.</description><identifier>ISSN: 0006-2952</identifier><identifier>EISSN: 1873-2968</identifier><identifier>DOI: 10.1016/0006-2952(86)90385-0</identifier><identifier>PMID: 2428377</identifier><language>eng</language><publisher>England: Elsevier Inc</publisher><subject>Arachidonic Acid ; Arachidonic Acids - pharmacology ; Breast Neoplasms - drug therapy ; Cell Count ; Cell Line ; Dipyridamole - therapeutic use ; Drug Synergism ; Female ; Humans ; Indomethacin - pharmacology ; Methotrexate - therapeutic use ; Polyglutamic Acid - metabolism ; Time Factors</subject><ispartof>Biochemical pharmacology, 1986-09, Vol.35 (18), p.3053-3056</ispartof><rights>1986</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/0006295286903850$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/2428377$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kennedy, D.G.</creatorcontrib><creatorcontrib>Van den Berg, H.W.</creatorcontrib><creatorcontrib>Clarke, R.</creatorcontrib><creatorcontrib>Murphy, R.F.</creatorcontrib><title>Enhancement of methotrexate cytotoxicity towards the MDA.MB.436 human breast cancer cell line by dipyridamole: The role of methotrexate polyglutamates</title><title>Biochemical pharmacology</title><addtitle>Biochem Pharmacol</addtitle><description>MTX and dipyridamole are synergistic in their toxicity towards the MDA.MB.436 human breast cancer cell line. Dipyridamole increases net MTX uptake into the cells and increases the intracellular levels of MTXG7 to G10, the highest molecular weight polyglutamyl derivatives of MTX detected. During a recovery period, after completion of exposure to MTX with and without dipyridamole, levels of MTXG7 to G10 remained elevated in dipyridamole treated cells by comparison with controls. Dipyridamole, which has no intrinsic effect on cell growth, transforms a cytostatic response of MDA.MB.436 cells towards MTX into a cytotoxic response. The effect of dipyridamole is not mediated through an increase in prostacyclin biosynthesis.</description><subject>Arachidonic Acid</subject><subject>Arachidonic Acids - pharmacology</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Cell Count</subject><subject>Cell Line</subject><subject>Dipyridamole - therapeutic use</subject><subject>Drug Synergism</subject><subject>Female</subject><subject>Humans</subject><subject>Indomethacin - pharmacology</subject><subject>Methotrexate - therapeutic use</subject><subject>Polyglutamic Acid - metabolism</subject><subject>Time Factors</subject><issn>0006-2952</issn><issn>1873-2968</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1986</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNplUclOwzAQtRAIyvIHIPkIhxQvwbE5IJVSFqmIC5wtx55QoyyV40LzI3wvCa24cJp5s897CJ1SMqaEiktCiEiYumLnUlwowuVVQnbQiMqM92Ehd9Hor-QAHbbtxwCloPton6VM8iwboe9ZvTC1hQrqiJsCVxAXTQywNhGw7WITm7W3PnY4Nl8muBbHBeDnu8n4-XaccoEXq8rUOA9g2ojtMCpgC2WJS18Dzjvs_LIL3pmqKeEav_bdoff-7Vo2ZfderqKpetQeo73ClC2cbO0RerufvU4fk_nLw9N0Mk-ACRoTJYV0VhWKFcowS5yiHJjMM5NCxhRTJAdjScpMnhJOUsMFL3ieppJTQZzjR-hsM3e5yitwehl8ZUKnt_z0-ZtNHvojPj0E3VoP_ZPOB7BRu8ZrSvSghx7Y1QPZWgr9q4cm_AczVX5n</recordid><startdate>19860915</startdate><enddate>19860915</enddate><creator>Kennedy, D.G.</creator><creator>Van den Berg, H.W.</creator><creator>Clarke, R.</creator><creator>Murphy, R.F.</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope></search><sort><creationdate>19860915</creationdate><title>Enhancement of methotrexate cytotoxicity towards the MDA.MB.436 human breast cancer cell line by dipyridamole: The role of methotrexate polyglutamates</title><author>Kennedy, D.G. ; Van den Berg, H.W. ; Clarke, R. ; Murphy, R.F.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-e261t-9868dc9f92f9a2c0d913e28b7a4e729290beac042ab40304a363f3b4483160dd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1986</creationdate><topic>Arachidonic Acid</topic><topic>Arachidonic Acids - pharmacology</topic><topic>Breast Neoplasms - drug therapy</topic><topic>Cell Count</topic><topic>Cell Line</topic><topic>Dipyridamole - therapeutic use</topic><topic>Drug Synergism</topic><topic>Female</topic><topic>Humans</topic><topic>Indomethacin - pharmacology</topic><topic>Methotrexate - therapeutic use</topic><topic>Polyglutamic Acid - metabolism</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kennedy, D.G.</creatorcontrib><creatorcontrib>Van den Berg, H.W.</creatorcontrib><creatorcontrib>Clarke, R.</creatorcontrib><creatorcontrib>Murphy, R.F.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>Biochemical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kennedy, D.G.</au><au>Van den Berg, H.W.</au><au>Clarke, R.</au><au>Murphy, R.F.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Enhancement of methotrexate cytotoxicity towards the MDA.MB.436 human breast cancer cell line by dipyridamole: The role of methotrexate polyglutamates</atitle><jtitle>Biochemical pharmacology</jtitle><addtitle>Biochem Pharmacol</addtitle><date>1986-09-15</date><risdate>1986</risdate><volume>35</volume><issue>18</issue><spage>3053</spage><epage>3056</epage><pages>3053-3056</pages><issn>0006-2952</issn><eissn>1873-2968</eissn><abstract>MTX and dipyridamole are synergistic in their toxicity towards the MDA.MB.436 human breast cancer cell line. Dipyridamole increases net MTX uptake into the cells and increases the intracellular levels of MTXG7 to G10, the highest molecular weight polyglutamyl derivatives of MTX detected. During a recovery period, after completion of exposure to MTX with and without dipyridamole, levels of MTXG7 to G10 remained elevated in dipyridamole treated cells by comparison with controls. Dipyridamole, which has no intrinsic effect on cell growth, transforms a cytostatic response of MDA.MB.436 cells towards MTX into a cytotoxic response. The effect of dipyridamole is not mediated through an increase in prostacyclin biosynthesis.</abstract><cop>England</cop><pub>Elsevier Inc</pub><pmid>2428377</pmid><doi>10.1016/0006-2952(86)90385-0</doi><tpages>4</tpages></addata></record> |
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subjects | Arachidonic Acid Arachidonic Acids - pharmacology Breast Neoplasms - drug therapy Cell Count Cell Line Dipyridamole - therapeutic use Drug Synergism Female Humans Indomethacin - pharmacology Methotrexate - therapeutic use Polyglutamic Acid - metabolism Time Factors |
title | Enhancement of methotrexate cytotoxicity towards the MDA.MB.436 human breast cancer cell line by dipyridamole: The role of methotrexate polyglutamates |
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