Inhibition of microtubule assembly is a possible mechanism of action of mitoxantrone
We have found that mitoxantrone can inhibit the polymerization of brain tubulinin a dose dependent manner. MXT had relatively high affinity for tubulin but had no appreciable effect on tubulin associated guanosinetriphosphatase (GTPase) activity nor could it compete with vinblastine(VB) and colchici...
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Veröffentlicht in: | Biochemical and biophysical research communications 1991-10, Vol.180 (1), p.118-123 |
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creator | Ho, Chi-Kuan Law, Sai-Lung Chiang, Hung Hsu, Mei-Ling Wang, Chien-Chia Wang, Sheng-Yuan |
description | We have found that mitoxantrone can inhibit the polymerization of brain tubulinin a dose dependent manner. MXT had relatively high affinity for tubulin but had no appreciable effect on tubulin associated guanosinetriphosphatase (GTPase) activity nor could it compete with vinblastine(VB) and colchicine (Col) for tubulin binding sites. Furthermore, MXT (0.1–10 μ M) is antiproliferative to cold-treated (0°C) epithelial cells afteronly brief exposure (30 min). These results indicated that MXTis amicrotubule inhibitory agent and can exert its anticellular effect through modulation of microtubule assembly. |
doi_str_mv | 10.1016/S0006-291X(05)81263-X |
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MXT had relatively high affinity for tubulin but had no appreciable effect on tubulin associated guanosinetriphosphatase (GTPase) activity nor could it compete with vinblastine(VB) and colchicine (Col) for tubulin binding sites. Furthermore, MXT (0.1–10 μ M) is antiproliferative to cold-treated (0°C) epithelial cells afteronly brief exposure (30 min). These results indicated that MXTis amicrotubule inhibitory agent and can exert its anticellular effect through modulation of microtubule assembly.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/S0006-291X(05)81263-X</identifier><identifier>PMID: 1930209</identifier><identifier>CODEN: BBRCA9</identifier><language>eng</language><publisher>San Diego, CA: Elsevier Inc</publisher><subject>Animals ; Antineoplastic agents ; Biological and medical sciences ; brain ; Brain - drug effects ; Brain - metabolism ; Cattle ; Col ; colchicine ; Colchicine - pharmacology ; DEAE ; diethylaminoethyl ; DMEM ; Dubelco minimal essential medium ; Electrophoresis, Polyacrylamide Gel ; General aspects ; GTP Phosphohydrolases - metabolism ; GTPase ; guanosinetriphosphatase ; Humans ; Immunoblotting ; KB Cells ; Medical sciences ; Microtubules - drug effects ; Microtubules - ultrastructure ; mitoxantrone ; Mitoxantrone - pharmacology ; MXT ; P-G buffer ; Pharmacology. Drug treatments ; phosphate-glutamate buffer ; thin layer chromatograpy ; TLC ; tubulin ; Tubulin - metabolism ; Tumor Cells, Cultured ; vinblastine ; Vinblastine - pharmacology</subject><ispartof>Biochemical and biophysical research communications, 1991-10, Vol.180 (1), p.118-123</ispartof><rights>1991 Academic Press, Inc.</rights><rights>1992 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c420t-ce60fc2e657b9515a74b95532db6144c839bb12293ce320a7c85e843d2d28a8c3</citedby><cites>FETCH-LOGICAL-c420t-ce60fc2e657b9515a74b95532db6144c839bb12293ce320a7c85e843d2d28a8c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0006-291X(05)81263-X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=5015170$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1930209$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ho, Chi-Kuan</creatorcontrib><creatorcontrib>Law, Sai-Lung</creatorcontrib><creatorcontrib>Chiang, Hung</creatorcontrib><creatorcontrib>Hsu, Mei-Ling</creatorcontrib><creatorcontrib>Wang, Chien-Chia</creatorcontrib><creatorcontrib>Wang, Sheng-Yuan</creatorcontrib><title>Inhibition of microtubule assembly is a possible mechanism of action of mitoxantrone</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>We have found that mitoxantrone can inhibit the polymerization of brain tubulinin a dose dependent manner. MXT had relatively high affinity for tubulin but had no appreciable effect on tubulin associated guanosinetriphosphatase (GTPase) activity nor could it compete with vinblastine(VB) and colchicine (Col) for tubulin binding sites. Furthermore, MXT (0.1–10 μ M) is antiproliferative to cold-treated (0°C) epithelial cells afteronly brief exposure (30 min). These results indicated that MXTis amicrotubule inhibitory agent and can exert its anticellular effect through modulation of microtubule assembly.</description><subject>Animals</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>brain</subject><subject>Brain - drug effects</subject><subject>Brain - metabolism</subject><subject>Cattle</subject><subject>Col</subject><subject>colchicine</subject><subject>Colchicine - pharmacology</subject><subject>DEAE</subject><subject>diethylaminoethyl</subject><subject>DMEM</subject><subject>Dubelco minimal essential medium</subject><subject>Electrophoresis, Polyacrylamide Gel</subject><subject>General aspects</subject><subject>GTP Phosphohydrolases - metabolism</subject><subject>GTPase</subject><subject>guanosinetriphosphatase</subject><subject>Humans</subject><subject>Immunoblotting</subject><subject>KB Cells</subject><subject>Medical sciences</subject><subject>Microtubules - drug effects</subject><subject>Microtubules - ultrastructure</subject><subject>mitoxantrone</subject><subject>Mitoxantrone - pharmacology</subject><subject>MXT</subject><subject>P-G buffer</subject><subject>Pharmacology. Drug treatments</subject><subject>phosphate-glutamate buffer</subject><subject>thin layer chromatograpy</subject><subject>TLC</subject><subject>tubulin</subject><subject>Tubulin - metabolism</subject><subject>Tumor Cells, Cultured</subject><subject>vinblastine</subject><subject>Vinblastine - pharmacology</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1991</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkMFO3DAQhq2KCra0j4CUA0LlkDJjx0l8QhUqLRJSDwVpb5btTISrJF7sBJW3r5ddwZHTSDPfPzP6GDtB-IaA9cUfAKhLrnD9FeR5i7wW5foDWyEoKDlCdcBWr8gR-5TSXwDEqlaH7BCVAA5qxe5upgdv_ezDVIS-GL2LYV7sMlBhUqLRDs-FT4UpNiElb3N7JPdgJp_GLW_cW3IO_8w0xzDRZ_axN0OiL_t6zO6vf9xd_Spvf_-8ufp-W7qKw1w6qqF3nGrZWCVRmqbKVQre2RqryrVCWYucK-FIcDCNayW1leh4x1vTOnHMznZ7NzE8LpRmPfrkaBjMRGFJuuFYV6DwXRDzPamUyKDcgVlDSpF6vYl-NPFZI-itdv2iXW-dapD6Rbte59zJ_sBiR-reUjvPeX66n5vkzNBHMzmfXjEJKLGBjF3uMMrWnjxFnZynyVHnI7lZd8G_88h_fIGfGg</recordid><startdate>19911015</startdate><enddate>19911015</enddate><creator>Ho, Chi-Kuan</creator><creator>Law, Sai-Lung</creator><creator>Chiang, Hung</creator><creator>Hsu, Mei-Ling</creator><creator>Wang, Chien-Chia</creator><creator>Wang, Sheng-Yuan</creator><general>Elsevier Inc</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>7QL</scope><scope>7TK</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>M81</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>19911015</creationdate><title>Inhibition of microtubule assembly is a possible mechanism of action of mitoxantrone</title><author>Ho, Chi-Kuan ; Law, Sai-Lung ; Chiang, Hung ; Hsu, Mei-Ling ; Wang, Chien-Chia ; Wang, Sheng-Yuan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c420t-ce60fc2e657b9515a74b95532db6144c839bb12293ce320a7c85e843d2d28a8c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1991</creationdate><topic>Animals</topic><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>brain</topic><topic>Brain - drug effects</topic><topic>Brain - metabolism</topic><topic>Cattle</topic><topic>Col</topic><topic>colchicine</topic><topic>Colchicine - pharmacology</topic><topic>DEAE</topic><topic>diethylaminoethyl</topic><topic>DMEM</topic><topic>Dubelco minimal essential medium</topic><topic>Electrophoresis, Polyacrylamide Gel</topic><topic>General aspects</topic><topic>GTP Phosphohydrolases - metabolism</topic><topic>GTPase</topic><topic>guanosinetriphosphatase</topic><topic>Humans</topic><topic>Immunoblotting</topic><topic>KB Cells</topic><topic>Medical sciences</topic><topic>Microtubules - drug effects</topic><topic>Microtubules - ultrastructure</topic><topic>mitoxantrone</topic><topic>Mitoxantrone - pharmacology</topic><topic>MXT</topic><topic>P-G buffer</topic><topic>Pharmacology. Drug treatments</topic><topic>phosphate-glutamate buffer</topic><topic>thin layer chromatograpy</topic><topic>TLC</topic><topic>tubulin</topic><topic>Tubulin - metabolism</topic><topic>Tumor Cells, Cultured</topic><topic>vinblastine</topic><topic>Vinblastine - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ho, Chi-Kuan</creatorcontrib><creatorcontrib>Law, Sai-Lung</creatorcontrib><creatorcontrib>Chiang, Hung</creatorcontrib><creatorcontrib>Hsu, Mei-Ling</creatorcontrib><creatorcontrib>Wang, Chien-Chia</creatorcontrib><creatorcontrib>Wang, Sheng-Yuan</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>Bacteriology Abstracts (Microbiology B)</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biochemistry Abstracts 3</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ho, Chi-Kuan</au><au>Law, Sai-Lung</au><au>Chiang, Hung</au><au>Hsu, Mei-Ling</au><au>Wang, Chien-Chia</au><au>Wang, Sheng-Yuan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of microtubule assembly is a possible mechanism of action of mitoxantrone</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>1991-10-15</date><risdate>1991</risdate><volume>180</volume><issue>1</issue><spage>118</spage><epage>123</epage><pages>118-123</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><coden>BBRCA9</coden><abstract>We have found that mitoxantrone can inhibit the polymerization of brain tubulinin a dose dependent manner. MXT had relatively high affinity for tubulin but had no appreciable effect on tubulin associated guanosinetriphosphatase (GTPase) activity nor could it compete with vinblastine(VB) and colchicine (Col) for tubulin binding sites. Furthermore, MXT (0.1–10 μ M) is antiproliferative to cold-treated (0°C) epithelial cells afteronly brief exposure (30 min). These results indicated that MXTis amicrotubule inhibitory agent and can exert its anticellular effect through modulation of microtubule assembly.</abstract><cop>San Diego, CA</cop><pub>Elsevier Inc</pub><pmid>1930209</pmid><doi>10.1016/S0006-291X(05)81263-X</doi><tpages>6</tpages></addata></record> |
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subjects | Animals Antineoplastic agents Biological and medical sciences brain Brain - drug effects Brain - metabolism Cattle Col colchicine Colchicine - pharmacology DEAE diethylaminoethyl DMEM Dubelco minimal essential medium Electrophoresis, Polyacrylamide Gel General aspects GTP Phosphohydrolases - metabolism GTPase guanosinetriphosphatase Humans Immunoblotting KB Cells Medical sciences Microtubules - drug effects Microtubules - ultrastructure mitoxantrone Mitoxantrone - pharmacology MXT P-G buffer Pharmacology. Drug treatments phosphate-glutamate buffer thin layer chromatograpy TLC tubulin Tubulin - metabolism Tumor Cells, Cultured vinblastine Vinblastine - pharmacology |
title | Inhibition of microtubule assembly is a possible mechanism of action of mitoxantrone |
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