Gossypol inhibits phosphorylation of Bcl-2 in human leukemia HL-60 cells
Gossypol is an attractive therapeutic anti-tumor agent as an apoptosis inducer and is being evaluated in preclinical tests. However, the molecular mechanisms underlying apoptosis induction by gossypol in malignant cells have not been completely enunciated. Here we investigate the alterations of Bcl-...
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| Veröffentlicht in: | European journal of pharmacology 2010-10, Vol.645 (1), p.9-13 |
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| creator | Huang, Li-heng Hu, Jia-qi Tao, Wei-qun Li, Yuan-hong Li, Guan-ming Xie, Pei-yi Liu, Xiao-shan Jiang, Jikai |
| description | Gossypol is an attractive therapeutic anti-tumor agent as an apoptosis inducer and is being evaluated in preclinical tests. However, the molecular mechanisms underlying apoptosis induction by gossypol in malignant cells have not been completely enunciated. Here we investigate the alterations of Bcl-2/Bcl-xL/Mcl-1 protein levels and Bcl-2 phosphorylation in gossypol-induced apoptosis in human leukemia HL-60 cells. We found that gossypol treatment inhibited cell growth and induced apoptosis in HL-60 cells. Bcl-2/Bcl-xL/Mcl-1 protein levels were slightly reduced and phosphorylation of Bcl-2 at threonine 56 (phospho T56) was not altered. However, phosphorylation of Bcl-2 at serine 70 (phospho S70) was strikingly down-regulated in gossypol-exposed cells. This reduction was found to be not only in both dose- and time-dependent fashion but also obviated by phorbol l2,13-dibutyrate (PDBu), an activator of protein kinase C (PKC). In addition, pre-treatment of PDBu partially prevented gossypol-induced apoptosis in HL-60 cells. Collectively, gossypol treatment can reduce phosphorylation of Bcl-2 at serine 70 in leukemia HL-60 cells and gossypol may be a promising therapeutical candidate for leukemia patients especially expressing phosphorylated Bcl-2 at Ser70. |
| doi_str_mv | 10.1016/j.ejphar.2010.06.070 |
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However, the molecular mechanisms underlying apoptosis induction by gossypol in malignant cells have not been completely enunciated. Here we investigate the alterations of Bcl-2/Bcl-xL/Mcl-1 protein levels and Bcl-2 phosphorylation in gossypol-induced apoptosis in human leukemia HL-60 cells. We found that gossypol treatment inhibited cell growth and induced apoptosis in HL-60 cells. Bcl-2/Bcl-xL/Mcl-1 protein levels were slightly reduced and phosphorylation of Bcl-2 at threonine 56 (phospho T56) was not altered. However, phosphorylation of Bcl-2 at serine 70 (phospho S70) was strikingly down-regulated in gossypol-exposed cells. This reduction was found to be not only in both dose- and time-dependent fashion but also obviated by phorbol l2,13-dibutyrate (PDBu), an activator of protein kinase C (PKC). In addition, pre-treatment of PDBu partially prevented gossypol-induced apoptosis in HL-60 cells. Collectively, gossypol treatment can reduce phosphorylation of Bcl-2 at serine 70 in leukemia HL-60 cells and gossypol may be a promising therapeutical candidate for leukemia patients especially expressing phosphorylated Bcl-2 at Ser70.</description><identifier>ISSN: 0014-2999</identifier><identifier>EISSN: 1879-0712</identifier><identifier>DOI: 10.1016/j.ejphar.2010.06.070</identifier><identifier>PMID: 20633548</identifier><identifier>CODEN: EJPHAZ</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>Antineoplastic Agents - pharmacology ; Apoptosis - drug effects ; Bcl-2 phosphorylation ; Biological and medical sciences ; Blotting, Western ; DNA Fragmentation - drug effects ; Dose-Response Relationship, Drug ; Down-Regulation ; Enzyme Activators - pharmacology ; Genes, bcl-2 ; Gossypol ; Gossypol - pharmacology ; Hematologic and hematopoietic diseases ; HL-60 Cells ; Humans ; Leukemia ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Medical sciences ; Pharmacology. Drug treatments ; Phorbol 12,13-Dibutyrate - pharmacology ; Phosphorylation ; Poly(ADP-ribose) Polymerases - metabolism ; Protein Kinase C - metabolism ; Proto-Oncogene Proteins c-bcl-2 - metabolism</subject><ispartof>European journal of pharmacology, 2010-10, Vol.645 (1), p.9-13</ispartof><rights>2010 Elsevier B.V.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright 2010 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c457t-5e825371b7b500a33479dc9de3c655be74316bb9515df4d98216ab7fc3ee30f83</citedby><cites>FETCH-LOGICAL-c457t-5e825371b7b500a33479dc9de3c655be74316bb9515df4d98216ab7fc3ee30f83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ejphar.2010.06.070$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23263623$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20633548$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Huang, Li-heng</creatorcontrib><creatorcontrib>Hu, Jia-qi</creatorcontrib><creatorcontrib>Tao, Wei-qun</creatorcontrib><creatorcontrib>Li, Yuan-hong</creatorcontrib><creatorcontrib>Li, Guan-ming</creatorcontrib><creatorcontrib>Xie, Pei-yi</creatorcontrib><creatorcontrib>Liu, Xiao-shan</creatorcontrib><creatorcontrib>Jiang, Jikai</creatorcontrib><title>Gossypol inhibits phosphorylation of Bcl-2 in human leukemia HL-60 cells</title><title>European journal of pharmacology</title><addtitle>Eur J Pharmacol</addtitle><description>Gossypol is an attractive therapeutic anti-tumor agent as an apoptosis inducer and is being evaluated in preclinical tests. However, the molecular mechanisms underlying apoptosis induction by gossypol in malignant cells have not been completely enunciated. Here we investigate the alterations of Bcl-2/Bcl-xL/Mcl-1 protein levels and Bcl-2 phosphorylation in gossypol-induced apoptosis in human leukemia HL-60 cells. We found that gossypol treatment inhibited cell growth and induced apoptosis in HL-60 cells. Bcl-2/Bcl-xL/Mcl-1 protein levels were slightly reduced and phosphorylation of Bcl-2 at threonine 56 (phospho T56) was not altered. However, phosphorylation of Bcl-2 at serine 70 (phospho S70) was strikingly down-regulated in gossypol-exposed cells. This reduction was found to be not only in both dose- and time-dependent fashion but also obviated by phorbol l2,13-dibutyrate (PDBu), an activator of protein kinase C (PKC). In addition, pre-treatment of PDBu partially prevented gossypol-induced apoptosis in HL-60 cells. Collectively, gossypol treatment can reduce phosphorylation of Bcl-2 at serine 70 in leukemia HL-60 cells and gossypol may be a promising therapeutical candidate for leukemia patients especially expressing phosphorylated Bcl-2 at Ser70.</description><subject>Antineoplastic Agents - pharmacology</subject><subject>Apoptosis - drug effects</subject><subject>Bcl-2 phosphorylation</subject><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>DNA Fragmentation - drug effects</subject><subject>Dose-Response Relationship, Drug</subject><subject>Down-Regulation</subject><subject>Enzyme Activators - pharmacology</subject><subject>Genes, bcl-2</subject><subject>Gossypol</subject><subject>Gossypol - pharmacology</subject><subject>Hematologic and hematopoietic diseases</subject><subject>HL-60 Cells</subject><subject>Humans</subject><subject>Leukemia</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Medical sciences</subject><subject>Pharmacology. Drug treatments</subject><subject>Phorbol 12,13-Dibutyrate - pharmacology</subject><subject>Phosphorylation</subject><subject>Poly(ADP-ribose) Polymerases - metabolism</subject><subject>Protein Kinase C - metabolism</subject><subject>Proto-Oncogene Proteins c-bcl-2 - metabolism</subject><issn>0014-2999</issn><issn>1879-0712</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEtrGzEQgEVJqB23_6CUvYSc1hlJK2l1CSQhiQuGXNKz0Gpnsdx9Vdot-N9Hxk5762EYGL55fYR8o7CmQOXtfo37cWfDmkEqgVyDgk9kSUulc1CUXZAlAC1yprVekKsY9wAgNBOfyYKB5FwU5ZJsXoYYD-PQZr7f-cpPMRt3Q0wRDq2d_NBnQ5M9uDZnich2c2f7rMX5F3beZpttLiFz2LbxC7lsbBvx6zmvyM_np7fHTb59ffnxeL_NXSHUlAssmeCKVqoSAJbzQuna6Rq5k0JUqApOZVVpQUXdFLUuGZW2Uo3jiByakq_IzWnuGIbfM8bJdD4eL7A9DnM0ShRAqeAskcWJdCH9GLAxY_CdDQdDwRwVmr05KTRHhQakSQpT2_fzgrnqsP7b9OEsAddnwEZn2ybY3vn4j-NMcsl44u5OHCYdfzwGE53H3mHtA7rJ1IP__yXv4QuPcg</recordid><startdate>20101025</startdate><enddate>20101025</enddate><creator>Huang, Li-heng</creator><creator>Hu, Jia-qi</creator><creator>Tao, Wei-qun</creator><creator>Li, Yuan-hong</creator><creator>Li, Guan-ming</creator><creator>Xie, Pei-yi</creator><creator>Liu, Xiao-shan</creator><creator>Jiang, Jikai</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>20101025</creationdate><title>Gossypol inhibits phosphorylation of Bcl-2 in human leukemia HL-60 cells</title><author>Huang, Li-heng ; Hu, Jia-qi ; Tao, Wei-qun ; Li, Yuan-hong ; Li, Guan-ming ; Xie, Pei-yi ; Liu, Xiao-shan ; Jiang, Jikai</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c457t-5e825371b7b500a33479dc9de3c655be74316bb9515df4d98216ab7fc3ee30f83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Antineoplastic Agents - pharmacology</topic><topic>Apoptosis - drug effects</topic><topic>Bcl-2 phosphorylation</topic><topic>Biological and medical sciences</topic><topic>Blotting, Western</topic><topic>DNA Fragmentation - drug effects</topic><topic>Dose-Response Relationship, Drug</topic><topic>Down-Regulation</topic><topic>Enzyme Activators - pharmacology</topic><topic>Genes, bcl-2</topic><topic>Gossypol</topic><topic>Gossypol - pharmacology</topic><topic>Hematologic and hematopoietic diseases</topic><topic>HL-60 Cells</topic><topic>Humans</topic><topic>Leukemia</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Medical sciences</topic><topic>Pharmacology. Drug treatments</topic><topic>Phorbol 12,13-Dibutyrate - pharmacology</topic><topic>Phosphorylation</topic><topic>Poly(ADP-ribose) Polymerases - metabolism</topic><topic>Protein Kinase C - metabolism</topic><topic>Proto-Oncogene Proteins c-bcl-2 - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Huang, Li-heng</creatorcontrib><creatorcontrib>Hu, Jia-qi</creatorcontrib><creatorcontrib>Tao, Wei-qun</creatorcontrib><creatorcontrib>Li, Yuan-hong</creatorcontrib><creatorcontrib>Li, Guan-ming</creatorcontrib><creatorcontrib>Xie, Pei-yi</creatorcontrib><creatorcontrib>Liu, Xiao-shan</creatorcontrib><creatorcontrib>Jiang, Jikai</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 pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Huang, Li-heng</au><au>Hu, Jia-qi</au><au>Tao, Wei-qun</au><au>Li, Yuan-hong</au><au>Li, Guan-ming</au><au>Xie, Pei-yi</au><au>Liu, Xiao-shan</au><au>Jiang, Jikai</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Gossypol inhibits phosphorylation of Bcl-2 in human leukemia HL-60 cells</atitle><jtitle>European journal of pharmacology</jtitle><addtitle>Eur J Pharmacol</addtitle><date>2010-10-25</date><risdate>2010</risdate><volume>645</volume><issue>1</issue><spage>9</spage><epage>13</epage><pages>9-13</pages><issn>0014-2999</issn><eissn>1879-0712</eissn><coden>EJPHAZ</coden><abstract>Gossypol is an attractive therapeutic anti-tumor agent as an apoptosis inducer and is being evaluated in preclinical tests. However, the molecular mechanisms underlying apoptosis induction by gossypol in malignant cells have not been completely enunciated. Here we investigate the alterations of Bcl-2/Bcl-xL/Mcl-1 protein levels and Bcl-2 phosphorylation in gossypol-induced apoptosis in human leukemia HL-60 cells. We found that gossypol treatment inhibited cell growth and induced apoptosis in HL-60 cells. Bcl-2/Bcl-xL/Mcl-1 protein levels were slightly reduced and phosphorylation of Bcl-2 at threonine 56 (phospho T56) was not altered. However, phosphorylation of Bcl-2 at serine 70 (phospho S70) was strikingly down-regulated in gossypol-exposed cells. This reduction was found to be not only in both dose- and time-dependent fashion but also obviated by phorbol l2,13-dibutyrate (PDBu), an activator of protein kinase C (PKC). In addition, pre-treatment of PDBu partially prevented gossypol-induced apoptosis in HL-60 cells. Collectively, gossypol treatment can reduce phosphorylation of Bcl-2 at serine 70 in leukemia HL-60 cells and gossypol may be a promising therapeutical candidate for leukemia patients especially expressing phosphorylated Bcl-2 at Ser70.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>20633548</pmid><doi>10.1016/j.ejphar.2010.06.070</doi><tpages>5</tpages></addata></record> |
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| subjects | Antineoplastic Agents - pharmacology Apoptosis - drug effects Bcl-2 phosphorylation Biological and medical sciences Blotting, Western DNA Fragmentation - drug effects Dose-Response Relationship, Drug Down-Regulation Enzyme Activators - pharmacology Genes, bcl-2 Gossypol Gossypol - pharmacology Hematologic and hematopoietic diseases HL-60 Cells Humans Leukemia Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Medical sciences Pharmacology. Drug treatments Phorbol 12,13-Dibutyrate - pharmacology Phosphorylation Poly(ADP-ribose) Polymerases - metabolism Protein Kinase C - metabolism Proto-Oncogene Proteins c-bcl-2 - metabolism |
| title | Gossypol inhibits phosphorylation of Bcl-2 in human leukemia HL-60 cells |
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