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Article: Id1, inhibitor of differentiation, is a key protein mediating anti-tumor responses of gamma-tocotrienol in breast cancer cells

TitleId1, inhibitor of differentiation, is a key protein mediating anti-tumor responses of gamma-tocotrienol in breast cancer cells
Authors
KeywordsBreast cancer
Chemosensatizing
Docetaxel
Id-1
Tocopherol
Tocotrienol
Vitamin E
Issue Date2010
PublisherElsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/canlet
Citation
Cancer Letters, 2010, v. 291 n. 2, p. 187-199 How to Cite?
AbstractGamma-tocotrienol has demonstrated anti-proliferative effect on breast cancer (BCa) cells, but mechanisms involved are largely unknown. This study aimed at deciphering the molecular pathways responsible for its activity. Our results showed that treatment of BCa cells with gamma-tocotrienol resulted in induction of apoptosis as evidenced by activation of pro-caspases, accumulation of sub-G1 cells and DNA fragmentations. Examination of the pro-survival genes revealed that the gamma-tocotrienol-induced cell death was associated with suppression of Id1 and NF-κB through modulation of their upstream regulators (Src, Smad1/5/8, Fak and LOX). Meanwhile, gamma-tocotrienol treatment also resulted in the induction of JNK signaling pathway and inhibition of JNK activity by specific inhibitor partially blocked the effect of gamma-tocotrienol. Furthermore, synergistic effect was observed when cells were co-treated with gamma-tocotrienol and Docetaxel. Interestingly, in cells that treated with gamma-tocotrienol, alpha-tocopherol or β-aminoproprionitrile were found to partially restore Id1 expression. Meanwhile, this restoration of Id1 was found to protect the cells from gamma-tocotrienol induced apoptosis. Consistent outcome was observed in cells ectopically transfected with the Id-1 gene. Our results suggested that the anti-proliferative and chemosensitization effect of gamma-tocotrienol on BCa cells may be mediated through downregulation of Id1 protein. © 2009 Elsevier Ireland Ltd. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/149737
ISSN
2023 Impact Factor: 9.1
2023 SCImago Journal Rankings: 2.595
ISI Accession Number ID
Funding AgencyGrant Number
Kuala Lumpur Kepong Berhad
RGCHKU 7314/01 M
HKU7490/03 M
7470/04 M
Funding Information:

This work was supported by research Grant from Kuala Lumpur Kepong Berhad to Davos Life Science Pte. Ltd. and RGC Grants to Y.C.W (HKU 7314/01 M, HKU7490/03 M and 7470/04 M).

References

 

DC FieldValueLanguage
dc.contributor.authorYap, WNen_US
dc.contributor.authorZaiden, Nen_US
dc.contributor.authorTan, YLen_US
dc.contributor.authorNgoh, CPen_US
dc.contributor.authorZhang, XWen_US
dc.contributor.authorWong, YCen_US
dc.contributor.authorLing, MTen_US
dc.contributor.authorYap, YLen_US
dc.date.accessioned2012-06-26T05:57:49Z-
dc.date.available2012-06-26T05:57:49Z-
dc.date.issued2010en_US
dc.identifier.citationCancer Letters, 2010, v. 291 n. 2, p. 187-199en_US
dc.identifier.issn0304-3835en_US
dc.identifier.urihttp://hdl.handle.net/10722/149737-
dc.description.abstractGamma-tocotrienol has demonstrated anti-proliferative effect on breast cancer (BCa) cells, but mechanisms involved are largely unknown. This study aimed at deciphering the molecular pathways responsible for its activity. Our results showed that treatment of BCa cells with gamma-tocotrienol resulted in induction of apoptosis as evidenced by activation of pro-caspases, accumulation of sub-G1 cells and DNA fragmentations. Examination of the pro-survival genes revealed that the gamma-tocotrienol-induced cell death was associated with suppression of Id1 and NF-κB through modulation of their upstream regulators (Src, Smad1/5/8, Fak and LOX). Meanwhile, gamma-tocotrienol treatment also resulted in the induction of JNK signaling pathway and inhibition of JNK activity by specific inhibitor partially blocked the effect of gamma-tocotrienol. Furthermore, synergistic effect was observed when cells were co-treated with gamma-tocotrienol and Docetaxel. Interestingly, in cells that treated with gamma-tocotrienol, alpha-tocopherol or β-aminoproprionitrile were found to partially restore Id1 expression. Meanwhile, this restoration of Id1 was found to protect the cells from gamma-tocotrienol induced apoptosis. Consistent outcome was observed in cells ectopically transfected with the Id-1 gene. Our results suggested that the anti-proliferative and chemosensitization effect of gamma-tocotrienol on BCa cells may be mediated through downregulation of Id1 protein. © 2009 Elsevier Ireland Ltd. All rights reserved.en_US
dc.languageengen_US
dc.publisherElsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/canleten_US
dc.relation.ispartofCancer Lettersen_US
dc.subjectBreast cancer-
dc.subjectChemosensatizing-
dc.subjectDocetaxel-
dc.subjectId-1-
dc.subjectTocopherol-
dc.subjectTocotrienol-
dc.subjectVitamin E-
dc.subject.meshAndrogens - Physiologyen_US
dc.subject.meshBreast Neoplasms - Drug Therapy - Genetics - Pathologyen_US
dc.subject.meshCell Death - Drug Effectsen_US
dc.subject.meshCell Differentiationen_US
dc.subject.meshCell Division - Drug Effectsen_US
dc.subject.meshChromans - Pharmacologyen_US
dc.subject.meshCollagenen_US
dc.subject.meshDna Fragmentationen_US
dc.subject.meshDown-Regulationen_US
dc.subject.meshDrug Combinationsen_US
dc.subject.meshEstrogens - Physiologyen_US
dc.subject.meshFemaleen_US
dc.subject.meshHumansen_US
dc.subject.meshIn Situ Nick-End Labelingen_US
dc.subject.meshInhibitor Of Differentiation Protein 1 - Genetics - Metabolismen_US
dc.subject.meshLamininen_US
dc.subject.meshMaleen_US
dc.subject.meshNeoplasm Invasivenessen_US
dc.subject.meshProstatic Neoplasms - Drug Therapy - Genetics - Pathologyen_US
dc.subject.meshProteoglycansen_US
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_US
dc.subject.meshTransfectionen_US
dc.subject.meshTumor Cells, Cultureden_US
dc.subject.meshVitamin E - Analogs & Derivatives - Pharmacologyen_US
dc.titleId1, inhibitor of differentiation, is a key protein mediating anti-tumor responses of gamma-tocotrienol in breast cancer cellsen_US
dc.typeArticleen_US
dc.identifier.emailWong, YC:ycwong@hkucc.hku.hken_US
dc.identifier.emailLing, MT:patling@hkucc.hku.hken_US
dc.identifier.authorityWong, YC=rp00316en_US
dc.identifier.authorityLing, MT=rp00449en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/j.canlet.2009.10.012en_US
dc.identifier.pmid19926394-
dc.identifier.scopuseid_2-s2.0-77950300003en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77950300003&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume291en_US
dc.identifier.issue2en_US
dc.identifier.spage187en_US
dc.identifier.epage199en_US
dc.identifier.isiWOS:000277547500007-
dc.publisher.placeIrelanden_US
dc.identifier.scopusauthoridYap, WN=25637949100en_US
dc.identifier.scopusauthoridZaiden, N=8360274200en_US
dc.identifier.scopusauthoridTan, YL=35148459300en_US
dc.identifier.scopusauthoridNgoh, CP=35148076100en_US
dc.identifier.scopusauthoridZhang, XW=16044335800en_US
dc.identifier.scopusauthoridWong, YC=7403041798en_US
dc.identifier.scopusauthoridLing, MT=7102229780en_US
dc.identifier.scopusauthoridYap, YL=7005551975en_US
dc.identifier.citeulike6212078-
dc.identifier.issnl0304-3835-

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