Antiproliferative effect of gossypol and its optical isomers on human reproductive cancer cell lines
The antiproliferative effect of gossypol and its optical isomers on various human cell lines of reproductive and nonreproductive tissue origin was studied. Various reproductive cancer cell lines of ovarian, gestational, and testicular origin were highly sensitive (IC50 values of 0.86–1.98) to gossyp...
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| Veröffentlicht in: | Gynecologic oncology 1989-03, Vol.32 (3), p.273-277 |
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| container_title | Gynecologic oncology |
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| creator | Band, Vimla Hoffer, Anita P. Band, Hamid Rhinehardt, Ann E. Knapp, Robert C. Matlin, Stephen A. Anderson, Deborah J. |
| description | The antiproliferative effect of gossypol and its optical isomers on various human cell lines of reproductive and nonreproductive tissue origin was studied. Various reproductive cancer cell lines of ovarian, gestational, and testicular origin were highly sensitive (IC50 values of 0.86–1.98) to gossypol. The antiproliferative action of gossypol was not restricted to reproductive cancers, as non-reproductive cancer cell lines were also equally sensitive (IC50 values of 0.69–3.55). In addition, actively proliferating untransformed cells such as fibroblasts and PHA-activated lymphocytes were also sensitive (IC50 values of 0.87–2.51). (−)-Gossypol was 3.6–12.4 times more potent than (+)-gossypol and 1.48–2.65 times more potent than (±)-gossypol. The most sensitive indicator of gossypol action was a decrease in DNA synthesis followed by inhibition of protein synthesis and uptake of rhodamine-123 by mitochondria as tested in an ovarian cancer cell line (OVCA 433) and a fibroblast line (Hs27). These results indicate that gossypol possesses a general nonselective antiproliferative action toward human cells
in vitro. Further, the pharmacologic activity of gossypol as an antiproliferative agent is primarily attributable to its (−) isomer, which is also the active isomer as a contraceptive. |
| doi_str_mv | 10.1016/0090-8258(89)90623-9 |
| format | Article |
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in vitro. Further, the pharmacologic activity of gossypol as an antiproliferative agent is primarily attributable to its (−) isomer, which is also the active isomer as a contraceptive.</description><identifier>ISSN: 0090-8258</identifier><identifier>EISSN: 1095-6859</identifier><identifier>DOI: 10.1016/0090-8258(89)90623-9</identifier><identifier>PMID: 2920946</identifier><identifier>CODEN: GYNOA3</identifier><language>eng</language><publisher>San Diego, CA: Elsevier Inc</publisher><subject>Antineoplastic agents ; Antineoplastic Agents - pharmacokinetics ; Biological and medical sciences ; Cell Division - drug effects ; Cell Line ; Chemotherapy ; DNA, Neoplasm - biosynthesis ; Dose-Response Relationship, Drug ; Female ; Fibroblasts - drug effects ; Fibroblasts - metabolism ; Fibroblasts - pathology ; Genital Neoplasms, Female - metabolism ; Genital Neoplasms, Female - pathology ; Genital Neoplasms, Male - metabolism ; Genital Neoplasms, Male - pathology ; Gossypol - analogs & derivatives ; Gossypol - pharmacology ; Humans ; Isomerism ; Leucine - metabolism ; Leukemia, Experimental - metabolism ; Leukemia, Experimental - pathology ; Male ; Medical sciences ; Mitochondria - metabolism ; Neoplasm Proteins - biosynthesis ; Pharmacology. Drug treatments ; Rhodamine 123 ; Rhodamines - pharmacokinetics</subject><ispartof>Gynecologic oncology, 1989-03, Vol.32 (3), p.273-277</ispartof><rights>1989</rights><rights>1989 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c386t-d98252fabc70577ac65cf5848173b7158b69a88f6ed8466f72511b3834b991fe3</citedby><cites>FETCH-LOGICAL-c386t-d98252fabc70577ac65cf5848173b7158b69a88f6ed8466f72511b3834b991fe3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/0090825889906239$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=7203199$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/2920946$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Band, Vimla</creatorcontrib><creatorcontrib>Hoffer, Anita P.</creatorcontrib><creatorcontrib>Band, Hamid</creatorcontrib><creatorcontrib>Rhinehardt, Ann E.</creatorcontrib><creatorcontrib>Knapp, Robert C.</creatorcontrib><creatorcontrib>Matlin, Stephen A.</creatorcontrib><creatorcontrib>Anderson, Deborah J.</creatorcontrib><title>Antiproliferative effect of gossypol and its optical isomers on human reproductive cancer cell lines</title><title>Gynecologic oncology</title><addtitle>Gynecol Oncol</addtitle><description>The antiproliferative effect of gossypol and its optical isomers on various human cell lines of reproductive and nonreproductive tissue origin was studied. Various reproductive cancer cell lines of ovarian, gestational, and testicular origin were highly sensitive (IC50 values of 0.86–1.98) to gossypol. The antiproliferative action of gossypol was not restricted to reproductive cancers, as non-reproductive cancer cell lines were also equally sensitive (IC50 values of 0.69–3.55). In addition, actively proliferating untransformed cells such as fibroblasts and PHA-activated lymphocytes were also sensitive (IC50 values of 0.87–2.51). (−)-Gossypol was 3.6–12.4 times more potent than (+)-gossypol and 1.48–2.65 times more potent than (±)-gossypol. The most sensitive indicator of gossypol action was a decrease in DNA synthesis followed by inhibition of protein synthesis and uptake of rhodamine-123 by mitochondria as tested in an ovarian cancer cell line (OVCA 433) and a fibroblast line (Hs27). These results indicate that gossypol possesses a general nonselective antiproliferative action toward human cells
in vitro. Further, the pharmacologic activity of gossypol as an antiproliferative agent is primarily attributable to its (−) isomer, which is also the active isomer as a contraceptive.</description><subject>Antineoplastic agents</subject><subject>Antineoplastic Agents - pharmacokinetics</subject><subject>Biological and medical sciences</subject><subject>Cell Division - drug effects</subject><subject>Cell Line</subject><subject>Chemotherapy</subject><subject>DNA, Neoplasm - biosynthesis</subject><subject>Dose-Response Relationship, Drug</subject><subject>Female</subject><subject>Fibroblasts - drug effects</subject><subject>Fibroblasts - metabolism</subject><subject>Fibroblasts - pathology</subject><subject>Genital Neoplasms, Female - metabolism</subject><subject>Genital Neoplasms, Female - pathology</subject><subject>Genital Neoplasms, Male - metabolism</subject><subject>Genital Neoplasms, Male - pathology</subject><subject>Gossypol - analogs & derivatives</subject><subject>Gossypol - pharmacology</subject><subject>Humans</subject><subject>Isomerism</subject><subject>Leucine - metabolism</subject><subject>Leukemia, Experimental - metabolism</subject><subject>Leukemia, Experimental - pathology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mitochondria - metabolism</subject><subject>Neoplasm Proteins - biosynthesis</subject><subject>Pharmacology. Drug treatments</subject><subject>Rhodamine 123</subject><subject>Rhodamines - pharmacokinetics</subject><issn>0090-8258</issn><issn>1095-6859</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1989</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMtKAzEUhoMotVbfQCELEV2MJnPJZSOU4g0KbnQdMpkTjcylJjOFvr2ZtnTpKoTznZ__fAhdUnJPCWUPhEiSiLQQt0LeScLSLJFHaEqJLBImCnmMpgfkFJ2F8EMIyQhNJ2iSypTInE1RNW97t_Jd7Sx43bs1YLAWTI87i7-6EDarrsa6rbDrA-5WvTO6xi50Dfj4b_H30OgWe4gZ1WC2AUa3Bjw2UNe4di2Ec3RidR3gYv_O0Ofz08fiNVm-v7wt5svEZIL1SSVj1dTq0nBScK4NK4wtRC4oz0pOC1EyqYWwDCqRM2Z5WlBaZiLLSymphWyGbna5sczvAKFXjQtjDd1CNwTFheCCEx7BfAcaH0_0YNXKu0b7jaJEjXLVaE6N5pSQaitXybh2tc8fygaqw9LeZpxf7-c6RE3WRxEuHDCekozKMeZxh0F0sXbgVTAOorPK-WheVZ37v8cfZZSWbQ</recordid><startdate>19890301</startdate><enddate>19890301</enddate><creator>Band, Vimla</creator><creator>Hoffer, Anita P.</creator><creator>Band, Hamid</creator><creator>Rhinehardt, Ann E.</creator><creator>Knapp, Robert C.</creator><creator>Matlin, Stephen A.</creator><creator>Anderson, Deborah J.</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>7X8</scope></search><sort><creationdate>19890301</creationdate><title>Antiproliferative effect of gossypol and its optical isomers on human reproductive cancer cell lines</title><author>Band, Vimla ; Hoffer, Anita P. ; Band, Hamid ; Rhinehardt, Ann E. ; Knapp, Robert C. ; Matlin, Stephen A. ; Anderson, Deborah J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c386t-d98252fabc70577ac65cf5848173b7158b69a88f6ed8466f72511b3834b991fe3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1989</creationdate><topic>Antineoplastic agents</topic><topic>Antineoplastic Agents - pharmacokinetics</topic><topic>Biological and medical sciences</topic><topic>Cell Division - drug effects</topic><topic>Cell Line</topic><topic>Chemotherapy</topic><topic>DNA, Neoplasm - biosynthesis</topic><topic>Dose-Response Relationship, Drug</topic><topic>Female</topic><topic>Fibroblasts - drug effects</topic><topic>Fibroblasts - metabolism</topic><topic>Fibroblasts - pathology</topic><topic>Genital Neoplasms, Female - metabolism</topic><topic>Genital Neoplasms, Female - pathology</topic><topic>Genital Neoplasms, Male - metabolism</topic><topic>Genital Neoplasms, Male - pathology</topic><topic>Gossypol - analogs & derivatives</topic><topic>Gossypol - pharmacology</topic><topic>Humans</topic><topic>Isomerism</topic><topic>Leucine - metabolism</topic><topic>Leukemia, Experimental - metabolism</topic><topic>Leukemia, Experimental - pathology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mitochondria - metabolism</topic><topic>Neoplasm Proteins - biosynthesis</topic><topic>Pharmacology. Drug treatments</topic><topic>Rhodamine 123</topic><topic>Rhodamines - pharmacokinetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Band, Vimla</creatorcontrib><creatorcontrib>Hoffer, Anita P.</creatorcontrib><creatorcontrib>Band, Hamid</creatorcontrib><creatorcontrib>Rhinehardt, Ann E.</creatorcontrib><creatorcontrib>Knapp, Robert C.</creatorcontrib><creatorcontrib>Matlin, Stephen A.</creatorcontrib><creatorcontrib>Anderson, Deborah 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>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Gynecologic oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Band, Vimla</au><au>Hoffer, Anita P.</au><au>Band, Hamid</au><au>Rhinehardt, Ann E.</au><au>Knapp, Robert C.</au><au>Matlin, Stephen A.</au><au>Anderson, Deborah J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antiproliferative effect of gossypol and its optical isomers on human reproductive cancer cell lines</atitle><jtitle>Gynecologic oncology</jtitle><addtitle>Gynecol Oncol</addtitle><date>1989-03-01</date><risdate>1989</risdate><volume>32</volume><issue>3</issue><spage>273</spage><epage>277</epage><pages>273-277</pages><issn>0090-8258</issn><eissn>1095-6859</eissn><coden>GYNOA3</coden><abstract>The antiproliferative effect of gossypol and its optical isomers on various human cell lines of reproductive and nonreproductive tissue origin was studied. Various reproductive cancer cell lines of ovarian, gestational, and testicular origin were highly sensitive (IC50 values of 0.86–1.98) to gossypol. The antiproliferative action of gossypol was not restricted to reproductive cancers, as non-reproductive cancer cell lines were also equally sensitive (IC50 values of 0.69–3.55). In addition, actively proliferating untransformed cells such as fibroblasts and PHA-activated lymphocytes were also sensitive (IC50 values of 0.87–2.51). (−)-Gossypol was 3.6–12.4 times more potent than (+)-gossypol and 1.48–2.65 times more potent than (±)-gossypol. The most sensitive indicator of gossypol action was a decrease in DNA synthesis followed by inhibition of protein synthesis and uptake of rhodamine-123 by mitochondria as tested in an ovarian cancer cell line (OVCA 433) and a fibroblast line (Hs27). These results indicate that gossypol possesses a general nonselective antiproliferative action toward human cells
in vitro. Further, the pharmacologic activity of gossypol as an antiproliferative agent is primarily attributable to its (−) isomer, which is also the active isomer as a contraceptive.</abstract><cop>San Diego, CA</cop><pub>Elsevier Inc</pub><pmid>2920946</pmid><doi>10.1016/0090-8258(89)90623-9</doi><tpages>5</tpages></addata></record> |
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| ispartof | Gynecologic oncology, 1989-03, Vol.32 (3), p.273-277 |
| issn | 0090-8258 1095-6859 |
| language | eng |
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| subjects | Antineoplastic agents Antineoplastic Agents - pharmacokinetics Biological and medical sciences Cell Division - drug effects Cell Line Chemotherapy DNA, Neoplasm - biosynthesis Dose-Response Relationship, Drug Female Fibroblasts - drug effects Fibroblasts - metabolism Fibroblasts - pathology Genital Neoplasms, Female - metabolism Genital Neoplasms, Female - pathology Genital Neoplasms, Male - metabolism Genital Neoplasms, Male - pathology Gossypol - analogs & derivatives Gossypol - pharmacology Humans Isomerism Leucine - metabolism Leukemia, Experimental - metabolism Leukemia, Experimental - pathology Male Medical sciences Mitochondria - metabolism Neoplasm Proteins - biosynthesis Pharmacology. Drug treatments Rhodamine 123 Rhodamines - pharmacokinetics |
| title | Antiproliferative effect of gossypol and its optical isomers on human reproductive cancer cell lines |
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