{"id":"https://openalex.org/W2171978272","doi":null,"title":"Sulindac metabolites induce caspase- and proteasome-dependent degradation of beta-catenin protein in human colon cancer cells.","display_name":"Sulindac metabolites induce caspase- and proteasome-dependent degradation of beta-catenin protein in human colon cancer cells.","publication_year":2003,"publication_date":"2003-09-01","ids":{"openalex":"https://openalex.org/W2171978272","mag":"2171978272","pmid":"https://pubmed.ncbi.nlm.nih.gov/14555707"},"language":"en","primary_location":{"id":"pmid:14555707","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/14555707","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Molecular cancer therapeutics","raw_type":"Journal Article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["pubmed"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5112906122","display_name":"Pamela L. Rice","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210087413","display_name":"University of Colorado Health","ror":"https://ror.org/0107w4315","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210087413"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Pamela L Rice","raw_affiliation_strings":["Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262, USA. pamela.rice@uchsc.edu"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262, USA. pamela.rice@uchsc.edu","institution_ids":["https://openalex.org/I4210087413"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5000225090","display_name":"Jennifer Kelloff","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Jennifer Kelloff","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5058754391","display_name":"Holly T. Sullivan","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Holly Sullivan","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5005452932","display_name":"Linda J Driggers","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Linda J Driggers","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":null,"display_name":"K Scott Beard","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"K Scott Beard","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5012555125","display_name":"Scott K. Kuwada","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Scott Kuwada","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5071802884","display_name":"Gary Anthony Piazza","orcid":"https://orcid.org/0000-0003-4418-887X","observed_orcids":["https://orcid.org/0000-0003-4418-887X"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Gary Piazza","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"last","author":{"id":"https://openalex.org/A5078332522","display_name":"Dennis J. Ahnen","orcid":"https://orcid.org/0000-0003-1783-1129","observed_orcids":["https://orcid.org/0000-0003-1783-1129"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Dennis J Ahnen","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":2.7347,"has_fulltext":false,"cited_by_count":100,"citation_normalized_percentile":{"value":0.91449013,"is_in_top_1_percent":false,"is_in_top_10_percent":true},"cited_by_percentile_year":{"min":88,"max":99},"biblio":{"volume":"2","issue":"9","first_page":"885","last_page":"92"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10929","display_name":"Wnt/\u03b2-catenin signaling in development and cancer","score":0.8964999914169312,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10929","display_name":"Wnt/\u03b2-catenin signaling in development and cancer","score":0.8964999914169312,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10678","display_name":"Inflammatory mediators and NSAID effects","score":0.08799999952316284,"subfield":{"id":"https://openalex.org/subfields/2736","display_name":"Pharmacology (medical)"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11067","display_name":"Colorectal Cancer Treatments and Studies","score":0.00279999990016222,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/sulindac","display_name":"sulindac","score":0.8970000147819519},{"id":"https://openalex.org/keywords/sulindac-sulfide","display_name":"sulindac sulfide","score":0.9639999866485596},{"id":"https://openalex.org/keywords/sulindac-sulfone","display_name":"sulindac sulfone","score":1.0},{"id":"https://openalex.org/keywords/beta-catenin-degradation","display_name":"\u03b2-catenin degradation","score":0.9049999713897705},{"id":"https://openalex.org/keywords/proteasome","display_name":"proteasome","score":0.6759999990463257},{"id":"https://openalex.org/keywords/caspase-activation","display_name":"caspase activation","score":0.9259999990463257},{"id":"https://openalex.org/keywords/apoptosis","display_name":"apoptosis","score":0.9879999756813049},{"id":"https://openalex.org/keywords/colon-cancer","display_name":"colon cancer","score":0.8069999814033508},{"id":"https://openalex.org/keywords/colorectal-cancer-chemoprevention","display_name":"colorectal cancer chemoprevention","score":0.828000009059906},{"id":"https://openalex.org/keywords/nonsteroidal-anti-inflammatory-drugs","display_name":"nonsteroidal anti-inflammatory drugs","score":0.9129999876022339},{"id":"https://openalex.org/keywords/cox-independent-mechanism","display_name":"COX-independent mechanism","score":0.7459999918937683},{"id":"https://openalex.org/keywords/apc-mutation","display_name":"APC mutation","score":0.9120000004768372},{"id":"https://openalex.org/keywords/cox-1","display_name":"cyclooxygenase-1","score":0.7039999961853027},{"id":"https://openalex.org/keywords/cyclooxygenase-2","display_name":"cyclooxygenase-2","score":1.0}],"concepts":[{"id":"https://openalex.org/C2776241388","wikidata":"https://www.wikidata.org/wiki/Q963093","display_name":"Sulindac","level":3,"score":0.9900680780410767},{"id":"https://openalex.org/C190283241","wikidata":"https://www.wikidata.org/wiki/Q14599311","display_name":"Apoptosis","level":2,"score":0.5406697392463684},{"id":"https://openalex.org/C27740335","wikidata":"https://www.wikidata.org/wiki/Q14878333","display_name":"Proteasome","level":2,"score":0.48076340556144714},{"id":"https://openalex.org/C30145163","wikidata":"https://www.wikidata.org/wiki/Q384104","display_name":"Catenin","level":4,"score":0.47333911061286926},{"id":"https://openalex.org/C2992195973","wikidata":"https://www.wikidata.org/wiki/Q33123","display_name":"Protein degradation","level":2,"score":0.47283536195755005},{"id":"https://openalex.org/C526805850","wikidata":"https://www.wikidata.org/wiki/Q188874","display_name":"Colorectal cancer","level":3,"score":0.4655962884426117},{"id":"https://openalex.org/C2778506107","wikidata":"https://www.wikidata.org/wiki/Q3272916","display_name":"MG132","level":4,"score":0.4490363597869873},{"id":"https://openalex.org/C2779324961","wikidata":"https://www.wikidata.org/wiki/Q1634046","display_name":"Beta-catenin","level":4,"score":0.4424273371696472},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.43975746631622314},{"id":"https://openalex.org/C2778367456","wikidata":"https://www.wikidata.org/wiki/Q7251235","display_name":"Proteasome inhibitor","level":3,"score":0.42340123653411865},{"id":"https://openalex.org/C31573885","wikidata":"https://www.wikidata.org/wiki/Q304484","display_name":"Programmed cell death","level":3,"score":0.41623345017433167},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.4074743390083313},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.40084901452064514},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.3159886598587036},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.26461923122406006},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.23728102445602417},{"id":"https://openalex.org/C137620995","wikidata":"https://www.wikidata.org/wiki/Q155769","display_name":"Wnt signaling pathway","level":3,"score":0.22228673100471497},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.13902029395103455},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.0696861743927002},{"id":"https://openalex.org/C2778484676","wikidata":"https://www.wikidata.org/wiki/Q20707196","display_name":"Nonsteroidal","level":2,"score":0.0}],"mesh":[{"descriptor_ui":"D000970","descriptor_name":"Antineoplastic Agents","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D002467","descriptor_name":"Cell Nucleus","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D003110","descriptor_name":"Colonic Neoplasms","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D003110","descriptor_name":"Colonic Neoplasms","qualifier_ui":"Q000473","qualifier_name":"pathology","is_major_topic":false},{"descriptor_ui":"D003546","descriptor_name":"Cysteine Endopeptidases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D003598","descriptor_name":"Cytoskeletal Proteins","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D004791","descriptor_name":"Enzyme Inhibitors","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D007976","descriptor_name":"Leupeptins","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D009097","descriptor_name":"Multienzyme Complexes","qualifier_ui":"Q000037","qualifier_name":"antagonists & inhibitors","is_major_topic":false},{"descriptor_ui":"D009097","descriptor_name":"Multienzyme Complexes","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D011125","descriptor_name":"Adenomatous Polyposis Coli","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D013467","descriptor_name":"Sulindac","qualifier_ui":"Q000031","qualifier_name":"analogs & derivatives","is_major_topic":true},{"descriptor_ui":"D013467","descriptor_name":"Sulindac","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D014407","descriptor_name":"Tumor Cells, Cultured","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D014407","descriptor_name":"Tumor Cells, Cultured","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D015398","descriptor_name":"Signal Transduction","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015534","descriptor_name":"Trans-Activators","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D015536","descriptor_name":"Down-Regulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015853","descriptor_name":"Cysteine Proteinase Inhibitors","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D017209","descriptor_name":"Apoptosis","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D020169","descriptor_name":"Caspases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D046988","descriptor_name":"Proteasome Endopeptidase Complex","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D051176","descriptor_name":"beta Catenin","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D053148","descriptor_name":"Caspase 3","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D061945","descriptor_name":"Caspase Inhibitors","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":2,"locations":[{"id":"pmid:14555707","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/14555707","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Molecular cancer therapeutics","raw_type":"Journal Article"},{"id":"mag:2171978272","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/14555707","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":null,"is_accepted":false,"is_published":false,"raw_source_name":"PubMed","raw_type":null}],"best_oa_location":null,"sustainable_development_goals":[{"display_name":"Good health and well-being","score":0.98580002784729,"id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":43,"referenced_works":["https://openalex.org/W140965324","https://openalex.org/W1497376376","https://openalex.org/W1556931007","https://openalex.org/W1584314654","https://openalex.org/W1607842260","https://openalex.org/W1775749144","https://openalex.org/W1822517393","https://openalex.org/W1966121721","https://openalex.org/W1967137553","https://openalex.org/W1979201752","https://openalex.org/W1989215255","https://openalex.org/W1999434816","https://openalex.org/W2002404925","https://openalex.org/W2007454357","https://openalex.org/W2008744347","https://openalex.org/W2014995450","https://openalex.org/W2026533505","https://openalex.org/W2026675621","https://openalex.org/W2038554369","https://openalex.org/W2044189814","https://openalex.org/W2045574895","https://openalex.org/W2050750704","https://openalex.org/W2054473882","https://openalex.org/W2081758458","https://openalex.org/W2081985759","https://openalex.org/W2087224686","https://openalex.org/W2095715712","https://openalex.org/W2103626309","https://openalex.org/W2109069210","https://openalex.org/W2109694492","https://openalex.org/W2111303192","https://openalex.org/W2112558428","https://openalex.org/W2117396468","https://openalex.org/W2118472471","https://openalex.org/W2125062544","https://openalex.org/W2152515299","https://openalex.org/W2154749163","https://openalex.org/W2156881931","https://openalex.org/W2161376238","https://openalex.org/W2161968975","https://openalex.org/W2318380017","https://openalex.org/W2338127681","https://openalex.org/W2616837541"],"related_works":["https://openalex.org/W1983812918","https://openalex.org/W2165332825","https://openalex.org/W2187902037","https://openalex.org/W1963871955","https://openalex.org/W6982571414","https://openalex.org/W2318723596","https://openalex.org/W2026650776","https://openalex.org/W2157920959","https://openalex.org/W2076865362","https://openalex.org/W1278199433"],"abstract_inverted_index":{"Colorectal":[0],"cancer":[1,9,113],"(CRC)":[2],"is":[3,18,224],"the":[4,12,31,59,100,144,159,246],"second":[5],"leading":[6],"cause":[7],"of":[8,15,40,61,83,94,102,110,119,132,137,146,166,206,217,234,242,248],"death":[10],"in":[11,21,30,185,201],"USA.":[13],"Accumulation":[14],"beta-catenin":[16,34,41,84,103,133,154,177,197,218,235],"protein":[17,104,134,155,219],"nearly":[19],"ubiquitous":[20],"colon":[22,75,112],"adenomas":[23],"and":[24,46,52,129,149,173,200,227,238],"cancers,":[25],"presumably":[26],"due":[27,231],"to":[28,98,152,232],"mutations":[29],"APC":[32,189,194],"or":[33,209],"genes":[35],"that":[36,50,203,215],"inhibit":[37,153],"proteasome-dependent":[38],"degradation":[39,178,237],"protein.":[42],"Substantial":[43],"clinical,":[44],"epidemiological,":[45],"animal":[47],"evidence":[48],"indicate":[49,214],"sulindac":[51,67,107,120,124,147,150,180,222],"other":[53],"non-steroidal":[54],"anti-inflammatory":[55],"drugs":[56],"(NSAIDs)":[57],"prevent":[58],"development":[60],"CRC.":[62],"The":[63,92],"mechanisms":[64],"by":[65,106,179,221],"which":[66],"exerts":[68],"its":[69],"potent":[70],"growth":[71],"inhibitory":[72],"effects":[73,183],"against":[74],"tumor":[76],"cells":[77,186,202],"are":[78],"incompletely":[79],"understood,":[80],"but":[81,195],"down-regulation":[82,105],"has":[85],"been":[86],"suggested":[87],"as":[88,168,170],"one":[89],"potential":[90],"mechanism.":[91],"goal":[93],"this":[95],"study":[96],"was":[97],"determine":[99],"mechanism":[101],"metabolites.":[108,181],"Treatment":[109],"human":[111],"cell":[114],"lines":[115],"with":[116,140,158,187,192],"apoptotic":[117],"concentrations":[118],"metabolites":[121,223],"(sulindac":[122],"sulfide,":[123],"sulfone)":[125],"induced":[126,220],"a":[127,240],"dose-":[128],"time-dependent":[130],"inhibition":[131],"expression.":[135,156],"Inhibition":[136],"proteasome":[138,236],"activity":[139],"MG-132":[141],"partially":[142,175,230,239],"blocked":[143,163],"ability":[145],"sulfide":[148],"sulfone":[151],"Pretreatment":[157],"caspase":[160,171,243],"inhibitor":[161],"z-VAD-fmk":[162],"morphological":[164],"signs":[165],"apoptosis":[167],"well":[169],"cleavage,":[172],"also":[174],"prevented":[176],"These":[182,212],"occurred":[184],"bi-allelic":[188],"mutation":[190,198],"(SW480),":[191],"wild-type":[193],"mono-allelic":[196],"(HCT116)":[199],"lack":[204],"expression":[205],"either":[207],"COX-1":[208],"-2":[210],"(HCT15).":[211],"results":[213],"loss":[216],"COX":[225],"independent":[226],"at":[228],"least":[229],"reactivation":[233],"result":[241],"activation":[244],"during":[245],"process":[247],"apoptosis.":[249]},"counts_by_year":[{"year":2025,"cited_by_count":1},{"year":2023,"cited_by_count":1},{"year":2022,"cited_by_count":1},{"year":2021,"cited_by_count":1},{"year":2020,"cited_by_count":1},{"year":2019,"cited_by_count":2},{"year":2017,"cited_by_count":4},{"year":2016,"cited_by_count":2},{"year":2015,"cited_by_count":4},{"year":2014,"cited_by_count":4},{"year":2013,"cited_by_count":11},{"year":2012,"cited_by_count":8}],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2016-06-24T00:00:00"}
