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Dual inhibition of tumor energy pathway by 2-deoxyglucose and metformin is effective against a broad spectrum of preclinical cancer models

DC Field Value Language
dc.contributor.author박은성-
dc.contributor.author정재호-
dc.date.accessioned2014-12-20T17:42:35Z-
dc.date.available2014-12-20T17:42:35Z-
dc.date.issued2011-
dc.identifier.issn1535-7163-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/95114-
dc.description.abstractTumor cell proliferation requires both growth signals and sufficient cellular bioenergetics. The AMP-activated protein kinase (AMPK) pathway seems dominant over the oncogenic signaling pathway suppressing cell proliferation. This study investigated the preclinical efficacy of targeting the tumor bioenergetic pathway using a glycolysis inhibitor 2-deoxyglucose (2DG) and AMPK agonists, AICAR and metformin. We evaluated the in vitro antitumor activity of 2DG, metformin or AICAR alone, and 2DG in combination either with metformin or AICAR. We examined in vivo efficacy using xenograft mouse models. 2DG alone was not sufficient to promote tumor cell death, reflecting the limited efficacy showed in clinical trials. A combined use of 2DG and AICAR also failed to induce cell death. However, 2DG and metformin led to significant cell death associated with decrease in cellular ATP, prolonged activation of AMPK, and sustained autophagy. Gene expression analysis and functional assays revealed that the selective AMPK agonist AICAR augments mitochondrial energy transduction (OXPHOS) whereas metformin compromises OXPHOS. Importantly, forced energy restoration with methyl pyruvate reversed the cell death induced by 2DG and metformin, suggesting a critical role of energetic deprivation in the underlying mechanism of cell death. The combination of 2DG and metformin inhibited tumor growth in mouse xenograft models. Deprivation of tumor bioenergetics by dual inhibition of energy pathways might be an effective novel therapeutic approach for a broad spectrum of human tumors-
dc.description.statementOfResponsibilityopen-
dc.format.extent2350~2362-
dc.relation.isPartOfMOLECULAR CANCER THERAPEUTICS-
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.MESHDeoxyglucose/administration & dosage-
dc.subject.MESHDeoxyglucose/therapeutic use*-
dc.subject.MESHDown-Regulation/drug effects-
dc.subject.MESHDrug Evaluation, Preclinical/methods-
dc.subject.MESHEnergy Metabolism/drug effects*-
dc.subject.MESHFemale-
dc.subject.MESHHumans-
dc.subject.MESHHypoglycemic Agents/administration & dosage-
dc.subject.MESHHypoglycemic Agents/therapeutic use-
dc.subject.MESHMetformin/administration & dosage-
dc.subject.MESHMetformin/therapeutic use*-
dc.subject.MESHMice-
dc.subject.MESHMice, Nude-
dc.subject.MESHNeoplasms/drug therapy*-
dc.subject.MESHNeoplasms/metabolism-
dc.subject.MESHSignal Transduction/drug effects-
dc.subject.MESHTreatment Outcome-
dc.subject.MESHTumor Cells, Cultured-
dc.subject.MESHXenograft Model Antitumor Assays-
dc.titleDual inhibition of tumor energy pathway by 2-deoxyglucose and metformin is effective against a broad spectrum of preclinical cancer models-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Surgery (외과학)-
dc.contributor.googleauthorJae-Ho Cheong-
dc.contributor.googleauthorEun Sung Park-
dc.contributor.googleauthorJiyong Liang-
dc.contributor.googleauthorJennifer B Dennison-
dc.contributor.googleauthorDimitra Tsavachidou-
dc.contributor.googleauthorCatherine Nguyen-Charles-
dc.contributor.googleauthorKwai Wa Cheng-
dc.contributor.googleauthorHassan Hall-
dc.contributor.googleauthorDong Zhang-
dc.contributor.googleauthorYiling Lu-
dc.contributor.googleauthorMurali Ravoori-
dc.contributor.googleauthorVikas Kundra-
dc.contributor.googleauthorJaffer Ajani-
dc.contributor.googleauthorJu-Seog Lee-
dc.contributor.googleauthorWaun Ki Hong-
dc.contributor.googleauthorGordon B Mills-
dc.identifier.doi10.1158/1535-7163.MCT-11-0497-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA01609-
dc.contributor.localIdA03717-
dc.relation.journalcodeJ02254-
dc.identifier.eissn1538-8514-
dc.identifier.pmid21992792-
dc.subject.keywordTumor bioenergetics-
dc.subject.keywordTargeted therapy-
dc.subject.keywordCancer energy metabolic pathway-
dc.contributor.alternativeNamePark, Eun Sung-
dc.contributor.alternativeNameCheong, Jae Ho-
dc.contributor.affiliatedAuthorPark, Eun Sung-
dc.contributor.affiliatedAuthorCheong, Jae Ho-
dc.rights.accessRightsfree-
dc.citation.volume10-
dc.citation.number12-
dc.citation.startPage2350-
dc.citation.endPage2362-
dc.identifier.bibliographicCitationMOLECULAR CANCER THERAPEUTICS, Vol.10(12) : 2350-2362, 2011-
dc.identifier.rimsid28104-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers

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