Elevated Levels of Cholesterol-Rich Lipid Rafts in Cancer Cells Are Correlated with Apoptosis Sensitivity Induced by Cholesterol-Depleting Agents
Lipid rafts/caveolae are membrane platforms for signaling molecules that regulate various cellular functions, including cell survival. To better understand the role of rafts in tumor progression and therapeutics, we investigated the effect of raft disruption on cell viability and compared raft level...
Gespeichert in:
| Veröffentlicht in: | The American journal of pathology 2006-04, Vol.168 (4), p.1107-1118 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1118 |
|---|---|
| container_issue | 4 |
| container_start_page | 1107 |
| container_title | The American journal of pathology |
| container_volume | 168 |
| creator | Li, Ying Chun Park, Mi Jung Ye, Sang-Kyu Kim, Chul-Woo Kim, Yong-Nyun |
| description | Lipid rafts/caveolae are membrane platforms for signaling molecules that regulate various cellular functions, including cell survival. To better understand the role of rafts in tumor progression and therapeutics, we investigated the effect of raft disruption on cell viability and compared raft levels in human cancer cell lines versus their normal counterparts. Here, we report that cholesterol depletion using methyl-β cyclodextrin caused anoikis-like apoptosis, which in A431 cells involved decreased raft levels, Bcl-xL down-regulation, caspase-3 activation, and Akt inactivation regardless of epidermal growth factor receptor activation. Cholesterol repletion replenished rafts on the cell surface and restored Akt activation and cell viability. Moreover, the breast cancer and the prostate cancer cell lines contained more lipid rafts and were more sensitive to cholesterol depletion-induced cell death than their normal counterparts. These results indicate that cancer cells contain increased levels of rafts and suggest a potential use of raft-modulating agents as anti-cancer drugs. |
| doi_str_mv | 10.2353/ajpath.2006.050959 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_1606567</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0002944010626909</els_id><sourcerecordid>67780639</sourcerecordid><originalsourceid>FETCH-LOGICAL-c540t-acfaaab8c33c06b02448e752334e98fd0c05d9a2ba34d2c28cd28b192a9144dc3</originalsourceid><addsrcrecordid>eNp9kt-K1DAUxoso7rj6Al5IbtSrjkma9A-IMNRVFwaEVa9DmpxOs2SammS6zGP4xmbs4Lo3XoWQ3_m-c86XLHtJ8JoWvHgnbycZhzXFuFxjjhvePMpWhFOeU9KQx9kKY0zzhjF8kT0L4TZdy6LGT7MLUvKSs7paZb-uLMwygkZbmMEG5HrUDs5CiOCdzW-MGtDWTEajG9nHgMyIWjkq8KgFm_iNB9Q678H-UbkzcUCbyU3RBRPQNxiDiWY28YiuR31QCemODxw-wmQhmnGHNjsYY3iePemlDfDifF5mPz5dfW-_5Nuvn6_bzTZXnOGYS9VLKbtaFYXCZYcpYzVUnBYFg6buNVaY60bSThZMU0VrpWndkYbKhjCmVXGZfVh0p0O3B62St5dWTN7spT8KJ414-DKaQezcLEiJ0_qqJPDmLODdz0MaR-xNUGkpcgR3CKKsqjotvEkgXUDlXQge-r8mBItTkmJJUpySFEuSqejVv-3dl5yjS8DrMyCDkrb3KRUT7rmqZJzXNHFvF24wu-HOeBBhL61NsuTkS8paMEEIPim-X8j0D2A24EVQBlLWOlWpKLQz_-v4N2KGzb8</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>67780639</pqid></control><display><type>article</type><title>Elevated Levels of Cholesterol-Rich Lipid Rafts in Cancer Cells Are Correlated with Apoptosis Sensitivity Induced by Cholesterol-Depleting Agents</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Li, Ying Chun ; Park, Mi Jung ; Ye, Sang-Kyu ; Kim, Chul-Woo ; Kim, Yong-Nyun</creator><creatorcontrib>Li, Ying Chun ; Park, Mi Jung ; Ye, Sang-Kyu ; Kim, Chul-Woo ; Kim, Yong-Nyun</creatorcontrib><description>Lipid rafts/caveolae are membrane platforms for signaling molecules that regulate various cellular functions, including cell survival. To better understand the role of rafts in tumor progression and therapeutics, we investigated the effect of raft disruption on cell viability and compared raft levels in human cancer cell lines versus their normal counterparts. Here, we report that cholesterol depletion using methyl-β cyclodextrin caused anoikis-like apoptosis, which in A431 cells involved decreased raft levels, Bcl-xL down-regulation, caspase-3 activation, and Akt inactivation regardless of epidermal growth factor receptor activation. Cholesterol repletion replenished rafts on the cell surface and restored Akt activation and cell viability. Moreover, the breast cancer and the prostate cancer cell lines contained more lipid rafts and were more sensitive to cholesterol depletion-induced cell death than their normal counterparts. These results indicate that cancer cells contain increased levels of rafts and suggest a potential use of raft-modulating agents as anti-cancer drugs.</description><identifier>ISSN: 0002-9440</identifier><identifier>EISSN: 1525-2191</identifier><identifier>DOI: 10.2353/ajpath.2006.050959</identifier><identifier>PMID: 16565487</identifier><identifier>CODEN: AJPAA4</identifier><language>eng</language><publisher>Bethesda, MD: Elsevier Inc</publisher><subject>Apoptosis - drug effects ; Apoptosis - physiology ; bcl-X Protein - metabolism ; beta-Cyclodextrins - pharmacology ; Biological and medical sciences ; Breast Neoplasms ; Carcinoma, Squamous Cell ; Caspase 3 ; Caspases - metabolism ; Cell Line, Tumor ; Cell Survival ; Cholesterol - metabolism ; Down-Regulation ; Enzyme Activation ; Female ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology ; Investigative techniques, diagnostic techniques (general aspects) ; Male ; Medical sciences ; Membrane Microdomains - drug effects ; Membrane Microdomains - metabolism ; Neoplasms - metabolism ; Neoplasms - pathology ; Neoplasms - ultrastructure ; Original Research Paper ; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques ; Prostatic Neoplasms ; Proto-Oncogene Proteins c-akt - metabolism ; Receptor, Epidermal Growth Factor - metabolism ; Signal Transduction ; Simvastatin - pharmacology</subject><ispartof>The American journal of pathology, 2006-04, Vol.168 (4), p.1107-1118</ispartof><rights>2006 American Society for Investigative Pathology</rights><rights>2006 INIST-CNRS</rights><rights>Copyright © American Society for Investigative Pathology 2006</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c540t-acfaaab8c33c06b02448e752334e98fd0c05d9a2ba34d2c28cd28b192a9144dc3</citedby><cites>FETCH-LOGICAL-c540t-acfaaab8c33c06b02448e752334e98fd0c05d9a2ba34d2c28cd28b192a9144dc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1606567/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://dx.doi.org/10.2353/ajpath.2006.050959$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,725,778,782,883,3539,27907,27908,45978,53774,53776</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17645582$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16565487$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Ying Chun</creatorcontrib><creatorcontrib>Park, Mi Jung</creatorcontrib><creatorcontrib>Ye, Sang-Kyu</creatorcontrib><creatorcontrib>Kim, Chul-Woo</creatorcontrib><creatorcontrib>Kim, Yong-Nyun</creatorcontrib><title>Elevated Levels of Cholesterol-Rich Lipid Rafts in Cancer Cells Are Correlated with Apoptosis Sensitivity Induced by Cholesterol-Depleting Agents</title><title>The American journal of pathology</title><addtitle>Am J Pathol</addtitle><description>Lipid rafts/caveolae are membrane platforms for signaling molecules that regulate various cellular functions, including cell survival. To better understand the role of rafts in tumor progression and therapeutics, we investigated the effect of raft disruption on cell viability and compared raft levels in human cancer cell lines versus their normal counterparts. Here, we report that cholesterol depletion using methyl-β cyclodextrin caused anoikis-like apoptosis, which in A431 cells involved decreased raft levels, Bcl-xL down-regulation, caspase-3 activation, and Akt inactivation regardless of epidermal growth factor receptor activation. Cholesterol repletion replenished rafts on the cell surface and restored Akt activation and cell viability. Moreover, the breast cancer and the prostate cancer cell lines contained more lipid rafts and were more sensitive to cholesterol depletion-induced cell death than their normal counterparts. These results indicate that cancer cells contain increased levels of rafts and suggest a potential use of raft-modulating agents as anti-cancer drugs.</description><subject>Apoptosis - drug effects</subject><subject>Apoptosis - physiology</subject><subject>bcl-X Protein - metabolism</subject><subject>beta-Cyclodextrins - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Breast Neoplasms</subject><subject>Carcinoma, Squamous Cell</subject><subject>Caspase 3</subject><subject>Caspases - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Cell Survival</subject><subject>Cholesterol - metabolism</subject><subject>Down-Regulation</subject><subject>Enzyme Activation</subject><subject>Female</subject><subject>Humans</subject><subject>Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Membrane Microdomains - drug effects</subject><subject>Membrane Microdomains - metabolism</subject><subject>Neoplasms - metabolism</subject><subject>Neoplasms - pathology</subject><subject>Neoplasms - ultrastructure</subject><subject>Original Research Paper</subject><subject>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</subject><subject>Prostatic Neoplasms</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Receptor, Epidermal Growth Factor - metabolism</subject><subject>Signal Transduction</subject><subject>Simvastatin - pharmacology</subject><issn>0002-9440</issn><issn>1525-2191</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kt-K1DAUxoso7rj6Al5IbtSrjkma9A-IMNRVFwaEVa9DmpxOs2SammS6zGP4xmbs4Lo3XoWQ3_m-c86XLHtJ8JoWvHgnbycZhzXFuFxjjhvePMpWhFOeU9KQx9kKY0zzhjF8kT0L4TZdy6LGT7MLUvKSs7paZb-uLMwygkZbmMEG5HrUDs5CiOCdzW-MGtDWTEajG9nHgMyIWjkq8KgFm_iNB9Q678H-UbkzcUCbyU3RBRPQNxiDiWY28YiuR31QCemODxw-wmQhmnGHNjsYY3iePemlDfDifF5mPz5dfW-_5Nuvn6_bzTZXnOGYS9VLKbtaFYXCZYcpYzVUnBYFg6buNVaY60bSThZMU0VrpWndkYbKhjCmVXGZfVh0p0O3B62St5dWTN7spT8KJ414-DKaQezcLEiJ0_qqJPDmLODdz0MaR-xNUGkpcgR3CKKsqjotvEkgXUDlXQge-r8mBItTkmJJUpySFEuSqejVv-3dl5yjS8DrMyCDkrb3KRUT7rmqZJzXNHFvF24wu-HOeBBhL61NsuTkS8paMEEIPim-X8j0D2A24EVQBlLWOlWpKLQz_-v4N2KGzb8</recordid><startdate>20060401</startdate><enddate>20060401</enddate><creator>Li, Ying Chun</creator><creator>Park, Mi Jung</creator><creator>Ye, Sang-Kyu</creator><creator>Kim, Chul-Woo</creator><creator>Kim, Yong-Nyun</creator><general>Elsevier Inc</general><general>ASIP</general><general>American Society for Investigative Pathology</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><scope>5PM</scope></search><sort><creationdate>20060401</creationdate><title>Elevated Levels of Cholesterol-Rich Lipid Rafts in Cancer Cells Are Correlated with Apoptosis Sensitivity Induced by Cholesterol-Depleting Agents</title><author>Li, Ying Chun ; Park, Mi Jung ; Ye, Sang-Kyu ; Kim, Chul-Woo ; Kim, Yong-Nyun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c540t-acfaaab8c33c06b02448e752334e98fd0c05d9a2ba34d2c28cd28b192a9144dc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Apoptosis - drug effects</topic><topic>Apoptosis - physiology</topic><topic>bcl-X Protein - metabolism</topic><topic>beta-Cyclodextrins - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Breast Neoplasms</topic><topic>Carcinoma, Squamous Cell</topic><topic>Caspase 3</topic><topic>Caspases - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Cell Survival</topic><topic>Cholesterol - metabolism</topic><topic>Down-Regulation</topic><topic>Enzyme Activation</topic><topic>Female</topic><topic>Humans</topic><topic>Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Membrane Microdomains - drug effects</topic><topic>Membrane Microdomains - metabolism</topic><topic>Neoplasms - metabolism</topic><topic>Neoplasms - pathology</topic><topic>Neoplasms - ultrastructure</topic><topic>Original Research Paper</topic><topic>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</topic><topic>Prostatic Neoplasms</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Receptor, Epidermal Growth Factor - metabolism</topic><topic>Signal Transduction</topic><topic>Simvastatin - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Ying Chun</creatorcontrib><creatorcontrib>Park, Mi Jung</creatorcontrib><creatorcontrib>Ye, Sang-Kyu</creatorcontrib><creatorcontrib>Kim, Chul-Woo</creatorcontrib><creatorcontrib>Kim, Yong-Nyun</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>The American journal of pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Ying Chun</au><au>Park, Mi Jung</au><au>Ye, Sang-Kyu</au><au>Kim, Chul-Woo</au><au>Kim, Yong-Nyun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Elevated Levels of Cholesterol-Rich Lipid Rafts in Cancer Cells Are Correlated with Apoptosis Sensitivity Induced by Cholesterol-Depleting Agents</atitle><jtitle>The American journal of pathology</jtitle><addtitle>Am J Pathol</addtitle><date>2006-04-01</date><risdate>2006</risdate><volume>168</volume><issue>4</issue><spage>1107</spage><epage>1118</epage><pages>1107-1118</pages><issn>0002-9440</issn><eissn>1525-2191</eissn><coden>AJPAA4</coden><abstract>Lipid rafts/caveolae are membrane platforms for signaling molecules that regulate various cellular functions, including cell survival. To better understand the role of rafts in tumor progression and therapeutics, we investigated the effect of raft disruption on cell viability and compared raft levels in human cancer cell lines versus their normal counterparts. Here, we report that cholesterol depletion using methyl-β cyclodextrin caused anoikis-like apoptosis, which in A431 cells involved decreased raft levels, Bcl-xL down-regulation, caspase-3 activation, and Akt inactivation regardless of epidermal growth factor receptor activation. Cholesterol repletion replenished rafts on the cell surface and restored Akt activation and cell viability. Moreover, the breast cancer and the prostate cancer cell lines contained more lipid rafts and were more sensitive to cholesterol depletion-induced cell death than their normal counterparts. These results indicate that cancer cells contain increased levels of rafts and suggest a potential use of raft-modulating agents as anti-cancer drugs.</abstract><cop>Bethesda, MD</cop><pub>Elsevier Inc</pub><pmid>16565487</pmid><doi>10.2353/ajpath.2006.050959</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0002-9440 |
| ispartof | The American journal of pathology, 2006-04, Vol.168 (4), p.1107-1118 |
| issn | 0002-9440 1525-2191 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_1606567 |
| source | MEDLINE; Elsevier ScienceDirect Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Apoptosis - drug effects Apoptosis - physiology bcl-X Protein - metabolism beta-Cyclodextrins - pharmacology Biological and medical sciences Breast Neoplasms Carcinoma, Squamous Cell Caspase 3 Caspases - metabolism Cell Line, Tumor Cell Survival Cholesterol - metabolism Down-Regulation Enzyme Activation Female Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology Investigative techniques, diagnostic techniques (general aspects) Male Medical sciences Membrane Microdomains - drug effects Membrane Microdomains - metabolism Neoplasms - metabolism Neoplasms - pathology Neoplasms - ultrastructure Original Research Paper Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques Prostatic Neoplasms Proto-Oncogene Proteins c-akt - metabolism Receptor, Epidermal Growth Factor - metabolism Signal Transduction Simvastatin - pharmacology |
| title | Elevated Levels of Cholesterol-Rich Lipid Rafts in Cancer Cells Are Correlated with Apoptosis Sensitivity Induced by Cholesterol-Depleting Agents |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-17T03%3A14%3A04IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Elevated%20Levels%20of%20Cholesterol-Rich%20Lipid%20Rafts%20in%20Cancer%20Cells%20Are%20Correlated%20with%20Apoptosis%20Sensitivity%20Induced%20by%20Cholesterol-Depleting%20Agents&rft.jtitle=The%20American%20journal%20of%20pathology&rft.au=Li,%20Ying%20Chun&rft.date=2006-04-01&rft.volume=168&rft.issue=4&rft.spage=1107&rft.epage=1118&rft.pages=1107-1118&rft.issn=0002-9440&rft.eissn=1525-2191&rft.coden=AJPAA4&rft_id=info:doi/10.2353/ajpath.2006.050959&rft_dat=%3Cproquest_pubme%3E67780639%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=67780639&rft_id=info:pmid/16565487&rft_els_id=S0002944010626909&rfr_iscdi=true |