In vivo effects of 4-amidinoindan-1-one 2'-amidinohydrazone (CGP 48664A) and α-difluoromethylornithine (DFMO) on L1210 growth, cell-cycle phase distribution and polyamine contents
We studied the in vivo effects of 4-amidinoindan-1-one 2'-amidinohydrazone (CGP 48664A), alpha-difluoromethylornithine (DFMO) and a combination of CGP 48664A-DFMO on tumor growth, cell-cycle phase distribution and polyamine contents. DBA-2 mice were inoculated i.p. with 10(5) L1210 cells on day...
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| Veröffentlicht in: | International journal of cancer 1995-09, Vol.62 (6), p.738-742 |
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| creator | DORHOUT, B TE VELDE, R. J FERWERDA, H KINGMA, A. W DE HOOG, E MUSKIET, F. A. J |
| description | We studied the in vivo effects of 4-amidinoindan-1-one 2'-amidinohydrazone (CGP 48664A), alpha-difluoromethylornithine (DFMO) and a combination of CGP 48664A-DFMO on tumor growth, cell-cycle phase distribution and polyamine contents. DBA-2 mice were inoculated i.p. with 10(5) L1210 cells on day 0, treated i.p. on days 1-4 and killed on day 5. As compared to controls, CGP 48664A, DFMO and the CGP 48664A-DFMO combination reduced L1210 cell numbers by 33, 43 and 85%, respectively. CGP 48664A did not affect cell-cycle phase distribution. DFMO and the CGP 48664A-DFMO combination caused a moderate and a heavy accumulation in G0/G1- and G2/M-phases, respectively. Compared with controls, the CGP 48664A-DFMO combination reduced putrescine, spermidine and total polyamines, but did not affect spermine. Compared with CGP 48664A, the CGP 48664A-DFMO combination caused lower putrescine and total polyamines, higher spermine, but no change in spermidine. Compared with DFMO, the CGP 48664A-DFMO combination caused higher putrescine and spermidine, lower spermine, but no change in total polyamine levels. We conclude that CGP 48664A potentiates the cystostatic effect of DFMO in vivo. The resulting growth inhibition is accompanied by an accumulation in G0/G1- and G2/M-phases and a reduction of putrescine and spermidine. The data suggest that perturbed polyamine composition rather than reduced spermidine or total polyamine pool size causes a profound growth inhibition. |
| doi_str_mv | 10.1002/ijc.2910620615 |
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J ; FERWERDA, H ; KINGMA, A. W ; DE HOOG, E ; MUSKIET, F. A. J</creator><creatorcontrib>DORHOUT, B ; TE VELDE, R. J ; FERWERDA, H ; KINGMA, A. W ; DE HOOG, E ; MUSKIET, F. A. J</creatorcontrib><description>We studied the in vivo effects of 4-amidinoindan-1-one 2'-amidinohydrazone (CGP 48664A), alpha-difluoromethylornithine (DFMO) and a combination of CGP 48664A-DFMO on tumor growth, cell-cycle phase distribution and polyamine contents. DBA-2 mice were inoculated i.p. with 10(5) L1210 cells on day 0, treated i.p. on days 1-4 and killed on day 5. As compared to controls, CGP 48664A, DFMO and the CGP 48664A-DFMO combination reduced L1210 cell numbers by 33, 43 and 85%, respectively. CGP 48664A did not affect cell-cycle phase distribution. DFMO and the CGP 48664A-DFMO combination caused a moderate and a heavy accumulation in G0/G1- and G2/M-phases, respectively. Compared with controls, the CGP 48664A-DFMO combination reduced putrescine, spermidine and total polyamines, but did not affect spermine. Compared with CGP 48664A, the CGP 48664A-DFMO combination caused lower putrescine and total polyamines, higher spermine, but no change in spermidine. Compared with DFMO, the CGP 48664A-DFMO combination caused higher putrescine and spermidine, lower spermine, but no change in total polyamine levels. We conclude that CGP 48664A potentiates the cystostatic effect of DFMO in vivo. The resulting growth inhibition is accompanied by an accumulation in G0/G1- and G2/M-phases and a reduction of putrescine and spermidine. The data suggest that perturbed polyamine composition rather than reduced spermidine or total polyamine pool size causes a profound growth inhibition.</description><identifier>ISSN: 0020-7136</identifier><identifier>EISSN: 1097-0215</identifier><identifier>DOI: 10.1002/ijc.2910620615</identifier><identifier>PMID: 7558423</identifier><identifier>CODEN: IJCNAW</identifier><language>eng</language><publisher>New York, NY: Wiley-Liss</publisher><subject>Adenosylmethionine Decarboxylase - antagonists & inhibitors ; Amidines - administration & dosage ; Amidines - pharmacology ; Animals ; Antineoplastic agents ; Antineoplastic Agents - administration & dosage ; Antineoplastic Agents - pharmacology ; Antineoplastic Combined Chemotherapy Protocols - pharmacology ; Biogenic Polyamines - metabolism ; Biological and medical sciences ; Cell Cycle - drug effects ; Cell Division - drug effects ; Eflornithine - administration & dosage ; Eflornithine - pharmacology ; Enzyme Inhibitors - pharmacology ; Female ; General aspects ; Indans - administration & dosage ; Indans - pharmacology ; Leukemia L1210 - drug therapy ; Leukemia L1210 - metabolism ; Leukemia L1210 - pathology ; Medical sciences ; Mice ; Mice, Inbred DBA ; Pharmacology. Drug treatments</subject><ispartof>International journal of cancer, 1995-09, Vol.62 (6), p.738-742</ispartof><rights>1995 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=3678880$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7558423$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>DORHOUT, B</creatorcontrib><creatorcontrib>TE VELDE, R. J</creatorcontrib><creatorcontrib>FERWERDA, H</creatorcontrib><creatorcontrib>KINGMA, A. W</creatorcontrib><creatorcontrib>DE HOOG, E</creatorcontrib><creatorcontrib>MUSKIET, F. A. J</creatorcontrib><title>In vivo effects of 4-amidinoindan-1-one 2'-amidinohydrazone (CGP 48664A) and α-difluoromethylornithine (DFMO) on L1210 growth, cell-cycle phase distribution and polyamine contents</title><title>International journal of cancer</title><addtitle>Int J Cancer</addtitle><description>We studied the in vivo effects of 4-amidinoindan-1-one 2'-amidinohydrazone (CGP 48664A), alpha-difluoromethylornithine (DFMO) and a combination of CGP 48664A-DFMO on tumor growth, cell-cycle phase distribution and polyamine contents. DBA-2 mice were inoculated i.p. with 10(5) L1210 cells on day 0, treated i.p. on days 1-4 and killed on day 5. As compared to controls, CGP 48664A, DFMO and the CGP 48664A-DFMO combination reduced L1210 cell numbers by 33, 43 and 85%, respectively. CGP 48664A did not affect cell-cycle phase distribution. DFMO and the CGP 48664A-DFMO combination caused a moderate and a heavy accumulation in G0/G1- and G2/M-phases, respectively. Compared with controls, the CGP 48664A-DFMO combination reduced putrescine, spermidine and total polyamines, but did not affect spermine. Compared with CGP 48664A, the CGP 48664A-DFMO combination caused lower putrescine and total polyamines, higher spermine, but no change in spermidine. Compared with DFMO, the CGP 48664A-DFMO combination caused higher putrescine and spermidine, lower spermine, but no change in total polyamine levels. We conclude that CGP 48664A potentiates the cystostatic effect of DFMO in vivo. The resulting growth inhibition is accompanied by an accumulation in G0/G1- and G2/M-phases and a reduction of putrescine and spermidine. The data suggest that perturbed polyamine composition rather than reduced spermidine or total polyamine pool size causes a profound growth inhibition.</description><subject>Adenosylmethionine Decarboxylase - antagonists & inhibitors</subject><subject>Amidines - administration & dosage</subject><subject>Amidines - pharmacology</subject><subject>Animals</subject><subject>Antineoplastic agents</subject><subject>Antineoplastic Agents - administration & dosage</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antineoplastic Combined Chemotherapy Protocols - pharmacology</subject><subject>Biogenic Polyamines - metabolism</subject><subject>Biological and medical sciences</subject><subject>Cell Cycle - drug effects</subject><subject>Cell Division - drug effects</subject><subject>Eflornithine - administration & dosage</subject><subject>Eflornithine - pharmacology</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Female</subject><subject>General aspects</subject><subject>Indans - administration & dosage</subject><subject>Indans - pharmacology</subject><subject>Leukemia L1210 - drug therapy</subject><subject>Leukemia L1210 - metabolism</subject><subject>Leukemia L1210 - pathology</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred DBA</subject><subject>Pharmacology. Drug treatments</subject><issn>0020-7136</issn><issn>1097-0215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1995</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kM1u1TAUhC0EKpfClh2SFwiohIuP4zjOsrr9odJFZQHrK9c_xFVip7ZTFN4KiefgmUjEhdWRZj7NHA1CL4GeAqXsg7_Tp6wFKhgVUD9CG6BtQyiD-jHaLAAlDVTiKXqW8x2lADXlR-ioqWvJWbVBv64DfvAPEVvnrC4ZR4c5UYM3PkQfjAoESAwWs7f_1G42Sf1YtXfbq8-YSyH42QlWweDfP4nxrp9iioMt3dzHFHzp_MqeX366OcEx4B0woPhbit9L9x5r2_dEz7q3eOxUttj4XJK_nYpf2DV0jP28VC8ZOoZiQ8nP0ROn-mxfHO4x-np58WX7kexurq63ZzsygmgKUa1lgle1q9vaMK0rxxR30lAOTIFTwOTqK6oF1VwZCRKY0HIZz7W0ddUxevM3d0zxfrK57Aef14dVsHHK-6apG14BXcBXB3C6HazZj8kPKs37w8yL__rgq6xV75IK2uf_WCUaKSWt_gD-rova</recordid><startdate>19950915</startdate><enddate>19950915</enddate><creator>DORHOUT, B</creator><creator>TE VELDE, R. J</creator><creator>FERWERDA, H</creator><creator>KINGMA, A. W</creator><creator>DE HOOG, E</creator><creator>MUSKIET, F. A. J</creator><general>Wiley-Liss</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>19950915</creationdate><title>In vivo effects of 4-amidinoindan-1-one 2'-amidinohydrazone (CGP 48664A) and α-difluoromethylornithine (DFMO) on L1210 growth, cell-cycle phase distribution and polyamine contents</title><author>DORHOUT, B ; TE VELDE, R. J ; FERWERDA, H ; KINGMA, A. W ; DE HOOG, E ; MUSKIET, F. A. J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p167t-a9e26435f595d2cc3f2a4f8d0412a1fa1282643a0c60c4ad818126c8021f909f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1995</creationdate><topic>Adenosylmethionine Decarboxylase - antagonists & inhibitors</topic><topic>Amidines - administration & dosage</topic><topic>Amidines - pharmacology</topic><topic>Animals</topic><topic>Antineoplastic agents</topic><topic>Antineoplastic Agents - administration & dosage</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antineoplastic Combined Chemotherapy Protocols - pharmacology</topic><topic>Biogenic Polyamines - metabolism</topic><topic>Biological and medical sciences</topic><topic>Cell Cycle - drug effects</topic><topic>Cell Division - drug effects</topic><topic>Eflornithine - administration & dosage</topic><topic>Eflornithine - pharmacology</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Female</topic><topic>General aspects</topic><topic>Indans - administration & dosage</topic><topic>Indans - pharmacology</topic><topic>Leukemia L1210 - drug therapy</topic><topic>Leukemia L1210 - metabolism</topic><topic>Leukemia L1210 - pathology</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred DBA</topic><topic>Pharmacology. Drug treatments</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>DORHOUT, B</creatorcontrib><creatorcontrib>TE VELDE, R. J</creatorcontrib><creatorcontrib>FERWERDA, H</creatorcontrib><creatorcontrib>KINGMA, A. W</creatorcontrib><creatorcontrib>DE HOOG, E</creatorcontrib><creatorcontrib>MUSKIET, F. A. J</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>MEDLINE - Academic</collection><jtitle>International journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>DORHOUT, B</au><au>TE VELDE, R. J</au><au>FERWERDA, H</au><au>KINGMA, A. W</au><au>DE HOOG, E</au><au>MUSKIET, F. A. J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In vivo effects of 4-amidinoindan-1-one 2'-amidinohydrazone (CGP 48664A) and α-difluoromethylornithine (DFMO) on L1210 growth, cell-cycle phase distribution and polyamine contents</atitle><jtitle>International journal of cancer</jtitle><addtitle>Int J Cancer</addtitle><date>1995-09-15</date><risdate>1995</risdate><volume>62</volume><issue>6</issue><spage>738</spage><epage>742</epage><pages>738-742</pages><issn>0020-7136</issn><eissn>1097-0215</eissn><coden>IJCNAW</coden><abstract>We studied the in vivo effects of 4-amidinoindan-1-one 2'-amidinohydrazone (CGP 48664A), alpha-difluoromethylornithine (DFMO) and a combination of CGP 48664A-DFMO on tumor growth, cell-cycle phase distribution and polyamine contents. DBA-2 mice were inoculated i.p. with 10(5) L1210 cells on day 0, treated i.p. on days 1-4 and killed on day 5. As compared to controls, CGP 48664A, DFMO and the CGP 48664A-DFMO combination reduced L1210 cell numbers by 33, 43 and 85%, respectively. CGP 48664A did not affect cell-cycle phase distribution. DFMO and the CGP 48664A-DFMO combination caused a moderate and a heavy accumulation in G0/G1- and G2/M-phases, respectively. Compared with controls, the CGP 48664A-DFMO combination reduced putrescine, spermidine and total polyamines, but did not affect spermine. Compared with CGP 48664A, the CGP 48664A-DFMO combination caused lower putrescine and total polyamines, higher spermine, but no change in spermidine. Compared with DFMO, the CGP 48664A-DFMO combination caused higher putrescine and spermidine, lower spermine, but no change in total polyamine levels. We conclude that CGP 48664A potentiates the cystostatic effect of DFMO in vivo. The resulting growth inhibition is accompanied by an accumulation in G0/G1- and G2/M-phases and a reduction of putrescine and spermidine. The data suggest that perturbed polyamine composition rather than reduced spermidine or total polyamine pool size causes a profound growth inhibition.</abstract><cop>New York, NY</cop><pub>Wiley-Liss</pub><pmid>7558423</pmid><doi>10.1002/ijc.2910620615</doi><tpages>5</tpages></addata></record> |
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| ispartof | International journal of cancer, 1995-09, Vol.62 (6), p.738-742 |
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| subjects | Adenosylmethionine Decarboxylase - antagonists & inhibitors Amidines - administration & dosage Amidines - pharmacology Animals Antineoplastic agents Antineoplastic Agents - administration & dosage Antineoplastic Agents - pharmacology Antineoplastic Combined Chemotherapy Protocols - pharmacology Biogenic Polyamines - metabolism Biological and medical sciences Cell Cycle - drug effects Cell Division - drug effects Eflornithine - administration & dosage Eflornithine - pharmacology Enzyme Inhibitors - pharmacology Female General aspects Indans - administration & dosage Indans - pharmacology Leukemia L1210 - drug therapy Leukemia L1210 - metabolism Leukemia L1210 - pathology Medical sciences Mice Mice, Inbred DBA Pharmacology. Drug treatments |
| title | In vivo effects of 4-amidinoindan-1-one 2'-amidinohydrazone (CGP 48664A) and α-difluoromethylornithine (DFMO) on L1210 growth, cell-cycle phase distribution and polyamine contents |
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