1 267

Cited 0 times in

Nonsteroidal anti-inflammatory drugs suppress cancer stem cells via inhibiting PTGS2 (cyclooxygenase 2) and NOTCH/HES1 and activating PPARG in colorectal cancer

DC FieldValueLanguage
dc.contributor.author천재희-
dc.contributor.author홍성필-
dc.contributor.author권지희-
dc.contributor.author김원호-
dc.contributor.author김지숙-
dc.contributor.author김태일-
dc.contributor.author문창모-
dc.contributor.author박재준-
dc.contributor.author이경진-
dc.date.accessioned2015-01-06T16:27:13Z-
dc.date.available2015-01-06T16:27:13Z-
dc.date.issued2014-
dc.identifier.issn0020-7136-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/98133-
dc.description.abstractCancer stem cells (CSCs) play a pivotal role in cancer relapse or metastasis. We investigated the CSC-suppressing effect of nonsteroidal anti-inflammatory drugs (NSAIDs) and the relevant mechanisms in colorectal cancer. We measured the effect of NSAIDs on CSC populations in Caco-2 or SW620 cells using colosphere formation and flow cytometric analysis of PROM1 (CD133)+CD44+ cells after indomethacin treatment with/without prostaglandin E2 (PGE2) or peroxisome proliferator-activated receptor γ (PPARG) antagonist, and examined the effect of indomethacin on transcriptional activity and protein expression of NOTCH/HES1 and PPARG. These effects of indomethacin were also evaluated in a xenograft mouse model. NSAIDs (indomethacin, sulindac and aspirin), celecoxib, γ-secretase inhibitor and PPARG agonist significantly decreased the number of colospheres formation compared to controls. In Caco-2 and SW620 cells, compared to controls, PROM1 (CD133)+CD44+ cells were significantly decreased by indomethacin treatment, and increased by 5-fluorouracil (5-FU) treatment. This 5-FU-induced increase of PROM1 (CD133)+CD44+ cells was significantly attenuated by combination with indomethacin. This CSC-inhibitory effect of indomethacin was reversed by addition of PGE2 and PPARG antagonist. Indomethacin significantly decreased CBFRE and increased PPRE transcriptional activity and their relative protein expressions. In xenograft mouse experiments using 5-FU-resistant SW620 cells, the 5-FU treatment combined with indomethacin significantly reduced tumor growth, compared to 5-FU alone. In addition, treatment of indomethacin alone or combination of 5-FU and indomethacin decreased the expressions of PROM1 (CD133), CD44, PTGS2 (cyclooxygenase 2) and HES1, and increased PPARG expression. NSAIDs could selectively reduce the colon CSCs and suppress 5-FU-induced increase of CSCs via inhibiting PTGS2 (cyclooxygenase 2) and NOTCH/HES1, and activating PPARG.-
dc.description.statementOfResponsibilityopen-
dc.format.extent519~529-
dc.relation.isPartOfINTERNATIONAL JOURNAL OF CANCER-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAnimals-
dc.subject.MESHAnti-Inflammatory Agents, Non-Steroidal/pharmacology*-
dc.subject.MESHBasic Helix-Loop-Helix Transcription Factors/antagonists & inhibitors*-
dc.subject.MESHCell Line, Tumor-
dc.subject.MESHColorectal Neoplasms/enzymology-
dc.subject.MESHColorectal Neoplasms/metabolism-
dc.subject.MESHColorectal Neoplasms/pathology*-
dc.subject.MESHCyclooxygenase 2/drug effects*-
dc.subject.MESHHomeodomain Proteins/antagonists & inhibitors*-
dc.subject.MESHHumans-
dc.subject.MESHMale-
dc.subject.MESHMice-
dc.subject.MESHMice, Inbred BALB C-
dc.subject.MESHNeoplastic Stem Cells/drug effects*-
dc.subject.MESHNeoplastic Stem Cells/enzymology-
dc.subject.MESHNeoplastic Stem Cells/metabolism-
dc.subject.MESHPPAR gamma/agonists*-
dc.subject.MESHReceptors, Notch/antagonists & inhibitors*-
dc.subject.MESHTranscription Factor HES-1-
dc.subject.MESHXenograft Model Antitumor Assays-
dc.titleNonsteroidal anti-inflammatory drugs suppress cancer stem cells via inhibiting PTGS2 (cyclooxygenase 2) and NOTCH/HES1 and activating PPARG in colorectal cancer-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentYonsei Biomedical Research Center (연세의생명연구원)-
dc.contributor.googleauthorChang Mo Moon-
dc.contributor.googleauthorJi-Hee Kwon-
dc.contributor.googleauthorJi Suk Kim-
dc.contributor.googleauthorSun-Hee Oh-
dc.contributor.googleauthorKyoung Jin Lee-
dc.contributor.googleauthorJae Jun Park-
dc.contributor.googleauthorSung Pil Hong-
dc.contributor.googleauthorJae Hee Cheon-
dc.contributor.googleauthorTae Il Kim-
dc.contributor.googleauthorWon Ho Kim-
dc.identifier.doi10.1002/ijc.2838-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA04404-
dc.contributor.localIdA00774-
dc.contributor.localIdA00971-
dc.contributor.localIdA01079-
dc.contributor.localIdA01390-
dc.contributor.localIdA01636-
dc.contributor.localIdA02657-
dc.contributor.localIdA04030-
dc.contributor.localIdA00254-
dc.relation.journalcodeJ01092-
dc.identifier.eissn1097-0215-
dc.identifier.pmid23852449-
dc.identifier.urlhttp://onlinelibrary.wiley.com/doi/10.1002/ijc.28381/abstract-
dc.subject.keywordNOTCH-
dc.subject.keywordPPARG-
dc.subject.keywordcolonic cancer stem cell-
dc.subject.keywordcyclooxygenase 2-
dc.subject.keywordnonsteroidal anti-inflammatory drugs-
dc.contributor.alternativeNameCheon, Jae Hee-
dc.contributor.alternativeNameHong, Sung Pil-
dc.contributor.alternativeNameKwon, Ji Hee-
dc.contributor.alternativeNameKim, Won Ho-
dc.contributor.alternativeNameKim, Ji Suk-
dc.contributor.alternativeNameKim, Tae Il-
dc.contributor.alternativeNameMoon, Chang Mo-
dc.contributor.alternativeNamePark, Jae Jun-
dc.contributor.alternativeNameLee, Kyoung Jin-
dc.contributor.affiliatedAuthorHong, Sung Pil-
dc.contributor.affiliatedAuthorKim, Won Ho-
dc.contributor.affiliatedAuthorKim, Ji Suk-
dc.contributor.affiliatedAuthorKim, Tae Il-
dc.contributor.affiliatedAuthorMoon, Chang Mo-
dc.contributor.affiliatedAuthorPark, Jae Jun-
dc.contributor.affiliatedAuthorLee, Kyoung Jin-
dc.contributor.affiliatedAuthorCheon, Jae Hee-
dc.contributor.affiliatedAuthorKwon. Ji Hee-
dc.rights.accessRightsfree-
dc.citation.volume134-
dc.citation.number3-
dc.citation.startPage519-
dc.citation.endPage529-
dc.identifier.bibliographicCitationINTERNATIONAL JOURNAL OF CANCER, Vol.134(3) : 519-529, 2014-
Appears in Collections:
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.