File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: All-trans retinoic acid can intensify the growth inhibition and differentiation induction effect of rosiglitazone on multiple myeloma cells

TitleAll-trans retinoic acid can intensify the growth inhibition and differentiation induction effect of rosiglitazone on multiple myeloma cells
Authors
KeywordsATRA
Caspase-3
Cell apoptosis
Cell differentiation
IAPs
Multiple myeloma
PPAR
Rosiglitazone
Issue Date2009
PublisherBlackwell Munksgaard. The Journal's web site is located at http://www.blackwellpublishing.com/journals/EJH
Citation
European Journal Of Haematology, 2009, v. 83 n. 3, p. 191-202 How to Cite?
AbstractObjective: Activation of PPAR by its ligands has shown potential anti-neoplastic effects in solid tumors. In this study, we investigate the effects of rosiglitazone (RGZ) alone as well as in combination with all trans-retinoic acid (ATRA) on human myeloma cell lines and try to address its potential mechanism. Methods: U266, RPMI-8226 and primary myeloma cells from patients were treated with different concentrations of RGZ in the presence or absence of ATRA and various biological responses were studied by the methods of [3H] thymidine incorporation, MTT, cell cycle analysis, Annexin V-PI staining, Wright-Giemsa staining, CD49e expression assay, light chain protein detection, RT-PCR and caspase-3 activity assay. Results: We report that exposure to RGZ induced proliferation inhibition and viability reduction in a dose-dependent manner in both U266 and RPMI-8226 cells. A similar exposure to RGZ also induced cell cycle arrest and cell apoptosis of myeloma cells. A combination of RGZ with ATRA enhanced the effects of RGZ and induced cell cycle arrest and apoptosis more profoundly in both cell lines. RGZ treated cells displayed morphological characteristics of cell differentiation, and more evident signs of differentiation were observed when combined with ATRA. These changes were confirmed by the detection of CD49e expression and light chain protein secretion. Similar cell apoptosis and differentiation were observed when primary CD138+ myeloma cells were treated with RGZ and ATRA. The mRNA expressions of FLIP, XIAP and survivin were detected in both cell lines and the levels decreased significantly after culture with RGZ. The addition of ATRA in culture medium made these changes more apparently. Caspase-3 activity was increased upon exposure to RGZ in both U266 and RPMI-8226 cells while combination of RGZ and ATRA brought out more effective activation of caspase-3. Similar apoptosis and cell differentiation induced by RGZ and ATRA can also be observed in primary CD138+ cells from myeloma patients. Conclusion: Concomitant RXR activation by ATRA enhanced the inhibitory effects of RGZ on myeloma cell proliferation, cell cycle, apoptosis and differentiation. Combination of RGZ and ATRA may be a useful therapy for human multiple myeloma. © 2009 John Wiley & Sons AS.
Persistent Identifierhttp://hdl.handle.net/10722/124998
ISSN
2015 Impact Factor: 2.544
2015 SCImago Journal Rankings: 1.180
ISI Accession Number ID
Funding AgencyGrant Number
Scientic Research Foundation of Health Ministry of Jiangsu ProvinceLJ200626
Funding Information:

The authors would like to thank Dr Jayanta Gupta (Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA) for critical review of the manuscript. This study was supported by grant LJ200626 from Scientic Research Foundation of Health Ministry of Jiangsu Province.

References

 

DC FieldValueLanguage
dc.contributor.authorHuang, Hen_HK
dc.contributor.authorWu, Den_HK
dc.contributor.authorFu, Jen_HK
dc.contributor.authorChen, Gen_HK
dc.contributor.authorChang, Wen_HK
dc.contributor.authorChow, HCHen_HK
dc.contributor.authorLeung, AYHen_HK
dc.contributor.authorLiang, Ren_HK
dc.date.accessioned2010-10-31T11:05:48Z-
dc.date.available2010-10-31T11:05:48Z-
dc.date.issued2009en_HK
dc.identifier.citationEuropean Journal Of Haematology, 2009, v. 83 n. 3, p. 191-202en_HK
dc.identifier.issn0902-4441en_HK
dc.identifier.urihttp://hdl.handle.net/10722/124998-
dc.description.abstractObjective: Activation of PPAR by its ligands has shown potential anti-neoplastic effects in solid tumors. In this study, we investigate the effects of rosiglitazone (RGZ) alone as well as in combination with all trans-retinoic acid (ATRA) on human myeloma cell lines and try to address its potential mechanism. Methods: U266, RPMI-8226 and primary myeloma cells from patients were treated with different concentrations of RGZ in the presence or absence of ATRA and various biological responses were studied by the methods of [3H] thymidine incorporation, MTT, cell cycle analysis, Annexin V-PI staining, Wright-Giemsa staining, CD49e expression assay, light chain protein detection, RT-PCR and caspase-3 activity assay. Results: We report that exposure to RGZ induced proliferation inhibition and viability reduction in a dose-dependent manner in both U266 and RPMI-8226 cells. A similar exposure to RGZ also induced cell cycle arrest and cell apoptosis of myeloma cells. A combination of RGZ with ATRA enhanced the effects of RGZ and induced cell cycle arrest and apoptosis more profoundly in both cell lines. RGZ treated cells displayed morphological characteristics of cell differentiation, and more evident signs of differentiation were observed when combined with ATRA. These changes were confirmed by the detection of CD49e expression and light chain protein secretion. Similar cell apoptosis and differentiation were observed when primary CD138+ myeloma cells were treated with RGZ and ATRA. The mRNA expressions of FLIP, XIAP and survivin were detected in both cell lines and the levels decreased significantly after culture with RGZ. The addition of ATRA in culture medium made these changes more apparently. Caspase-3 activity was increased upon exposure to RGZ in both U266 and RPMI-8226 cells while combination of RGZ and ATRA brought out more effective activation of caspase-3. Similar apoptosis and cell differentiation induced by RGZ and ATRA can also be observed in primary CD138+ cells from myeloma patients. Conclusion: Concomitant RXR activation by ATRA enhanced the inhibitory effects of RGZ on myeloma cell proliferation, cell cycle, apoptosis and differentiation. Combination of RGZ and ATRA may be a useful therapy for human multiple myeloma. © 2009 John Wiley & Sons AS.en_HK
dc.languageengen_HK
dc.publisherBlackwell Munksgaard. The Journal's web site is located at http://www.blackwellpublishing.com/journals/EJHen_HK
dc.relation.ispartofEuropean Journal of Haematologyen_HK
dc.rightsThe definitive version is available at www.blackwell-synergy.com-
dc.subjectATRAen_HK
dc.subjectCaspase-3en_HK
dc.subjectCell apoptosisen_HK
dc.subjectCell differentiationen_HK
dc.subjectIAPsen_HK
dc.subjectMultiple myelomaen_HK
dc.subjectPPARen_HK
dc.subjectRosiglitazoneen_HK
dc.subject.meshAged-
dc.subject.meshApoptosis-
dc.subject.meshMultiple Myeloma - drug therapy - pathology-
dc.subject.meshThiazolidinediones - pharmacology-
dc.subject.meshTretinoin - pharmacology-
dc.titleAll-trans retinoic acid can intensify the growth inhibition and differentiation induction effect of rosiglitazone on multiple myeloma cellsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0902-4441&volume=83&issue=3&spage=191–202&epage=&date=2009&atitle=All-trans+retinoic+acid+can+intensify+the+growth+inhibition+and+differentiation+induction+effect+of+rosiglitazone+on+multiple+myeloma+cellsen_HK
dc.identifier.emailLeung, AYH:ayhleung@hku.hken_HK
dc.identifier.emailLiang, R:rliang@hku.hken_HK
dc.identifier.authorityLeung, AYH=rp00265en_HK
dc.identifier.authorityLiang, R=rp00345en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1111/j.1600-0609.2009.01277.xen_HK
dc.identifier.pmid19467017-
dc.identifier.scopuseid_2-s2.0-68849097535en_HK
dc.identifier.hkuros180429en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-68849097535&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume83en_HK
dc.identifier.issue3en_HK
dc.identifier.spage191en_HK
dc.identifier.epage202en_HK
dc.identifier.isiWOS:000268684100004-
dc.publisher.placeDenmarken_HK
dc.identifier.scopusauthoridHuang, H=26023212400en_HK
dc.identifier.scopusauthoridWu, D=23471117100en_HK
dc.identifier.scopusauthoridFu, J=15076677800en_HK
dc.identifier.scopusauthoridChen, G=7406543262en_HK
dc.identifier.scopusauthoridChang, W=8449929200en_HK
dc.identifier.scopusauthoridChow, HCH=7102303391en_HK
dc.identifier.scopusauthoridLeung, AYH=7403012668en_HK
dc.identifier.scopusauthoridLiang, R=26643224900en_HK
dc.identifier.citeulike5401227-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats