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Article: LDH-A silencing suppresses breast cancer tumorigenicity through induction of oxidative stress mediated mitochondrial pathway apoptosis

TitleLDH-A silencing suppresses breast cancer tumorigenicity through induction of oxidative stress mediated mitochondrial pathway apoptosis
Authors
KeywordsApoptosis
Breast cancer
LDH-A
Mitochondrion
Oxidative stress
Issue Date2012
PublisherSpringer New York LLC. The Journal's web site is located at http://springerlink.metapress.com/openurl.asp?genre=journal&issn=0167-6806
Citation
Breast Cancer Research And Treatment, 2012, v. 131 n. 3, p. 791-800 How to Cite?
AbstractLDH-A, as the critical enzyme accounting for the transformation from pyruvate into lactate, has been demonstrated to be highly expressed in various cancer cells and its silencing has also been approved relating to increased apoptosis in lymphoma cells. In this study, we intend to investigate the correlation between LDH-A and other clinicopathological factors of breast cancer and whether LDH-A silencing could suppress breast cancer growth, and if so the potential mechanisms. 46 breast cancer specimens were collected to study the relation between LDH-A expression and clinicopathological characteristics including menopause, tumor size, node involvement, differentiation, and pathological subtypes classified by ER, PR, and Her-2. shRNAs were designed and applied to silence LDH-A expression in breast cancer cell lines MCF-7 and MDA-MB-231. The effects of LDH-A reduction on cancer cells were studied by a series of in vitro and in vivo experiments, including cell growth assay, apoptosis evaluation, oxidative stress detection, transmission electron microscopy observation, and tumor formation assay on nude mice. LDH-A expression was found to correlate significantly with tumor size and to be independent for other clinicopathological factors. LDH-A reduction resulted in an inhibited cancer cell proliferation, elevated intracellular oxidative stress, and induction of mitochondrial pathway apoptosis. Meanwhile, the tumorigenic ability of LDH-A deficient cancer cells was significantly limited in both breast cancer xenografts. The Ki67 positive cancer cells were significantly reduced in LDH-A deficiency tumor samples, while the apoptosis ratio was enhanced. Our results suggested that LDH-A inhibition might offer a promising therapeutic strategy for breast cancer. © 2011 Springer Science+Business Media, LLC.
Persistent Identifierhttp://hdl.handle.net/10722/137125
ISSN
2015 Impact Factor: 4.085
2015 SCImago Journal Rankings: 2.424
ISI Accession Number ID
Funding AgencyGrant Number
University of Hong Kong
Funding Information:

We thank Vicki Geall in the Department of Research Service in The University of Hong Kong for editorial assistance. We also appreciate the great help from The Electronic Microscope Unit in The University of Hong Kong. This research was funded by seed fundings from The University of Hong Kong.

References

 

DC FieldValueLanguage
dc.contributor.authorWang, ZYen_HK
dc.contributor.authorLoo, TYen_HK
dc.contributor.authorShen, JGen_HK
dc.contributor.authorWang, Nen_HK
dc.contributor.authorWang, DMen_HK
dc.contributor.authorYang, DPen_HK
dc.contributor.authorMo, SLen_HK
dc.contributor.authorGuan, XYen_HK
dc.contributor.authorChen, JPen_HK
dc.date.accessioned2011-08-23T01:59:42Z-
dc.date.available2011-08-23T01:59:42Z-
dc.date.issued2012en_HK
dc.identifier.citationBreast Cancer Research And Treatment, 2012, v. 131 n. 3, p. 791-800en_HK
dc.identifier.issn0167-6806en_HK
dc.identifier.urihttp://hdl.handle.net/10722/137125-
dc.description.abstractLDH-A, as the critical enzyme accounting for the transformation from pyruvate into lactate, has been demonstrated to be highly expressed in various cancer cells and its silencing has also been approved relating to increased apoptosis in lymphoma cells. In this study, we intend to investigate the correlation between LDH-A and other clinicopathological factors of breast cancer and whether LDH-A silencing could suppress breast cancer growth, and if so the potential mechanisms. 46 breast cancer specimens were collected to study the relation between LDH-A expression and clinicopathological characteristics including menopause, tumor size, node involvement, differentiation, and pathological subtypes classified by ER, PR, and Her-2. shRNAs were designed and applied to silence LDH-A expression in breast cancer cell lines MCF-7 and MDA-MB-231. The effects of LDH-A reduction on cancer cells were studied by a series of in vitro and in vivo experiments, including cell growth assay, apoptosis evaluation, oxidative stress detection, transmission electron microscopy observation, and tumor formation assay on nude mice. LDH-A expression was found to correlate significantly with tumor size and to be independent for other clinicopathological factors. LDH-A reduction resulted in an inhibited cancer cell proliferation, elevated intracellular oxidative stress, and induction of mitochondrial pathway apoptosis. Meanwhile, the tumorigenic ability of LDH-A deficient cancer cells was significantly limited in both breast cancer xenografts. The Ki67 positive cancer cells were significantly reduced in LDH-A deficiency tumor samples, while the apoptosis ratio was enhanced. Our results suggested that LDH-A inhibition might offer a promising therapeutic strategy for breast cancer. © 2011 Springer Science+Business Media, LLC.en_HK
dc.languageeng-
dc.publisherSpringer New York LLC. The Journal's web site is located at http://springerlink.metapress.com/openurl.asp?genre=journal&issn=0167-6806en_HK
dc.relation.ispartofBreast Cancer Research and Treatmenten_HK
dc.rightsThe original publication is available at www.springerlink.com-
dc.subjectApoptosisen_HK
dc.subjectBreast canceren_HK
dc.subjectLDH-Aen_HK
dc.subjectMitochondrionen_HK
dc.subjectOxidative stressen_HK
dc.titleLDH-A silencing suppresses breast cancer tumorigenicity through induction of oxidative stress mediated mitochondrial pathway apoptosisen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0167-6806&volume=&spage=&epage=&date=2011&atitle=LDH-A+silencing+suppresses+breast+cancer+tumorigenicity+through+induction+of+oxidative+stress+mediated+mitochondrial+pathway+apoptosis-
dc.identifier.emailShen, JG: shenjg@hku.hken_HK
dc.identifier.emailGuan, XY: xyguan@hkucc.hku.hken_HK
dc.identifier.emailChen, JP: abchen@hku.hken_HK
dc.identifier.authorityShen, JG=rp00487en_HK
dc.identifier.authorityGuan, XY=rp00454en_HK
dc.identifier.authorityChen, JP=rp01316en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1007/s10549-011-1466-6en_HK
dc.identifier.pmid21452021-
dc.identifier.scopuseid_2-s2.0-84856213516en_HK
dc.identifier.hkuros189748-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84856213516&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume131en_HK
dc.identifier.issue3en_HK
dc.identifier.spage791en_HK
dc.identifier.epage800en_HK
dc.identifier.eissn1573-7217-
dc.identifier.isiWOS:000299346100006-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridWang, ZY=7410054221en_HK
dc.identifier.scopusauthoridLoo, TY=7006008583en_HK
dc.identifier.scopusauthoridShen, JG=7404929947en_HK
dc.identifier.scopusauthoridWang, N=16311384500en_HK
dc.identifier.scopusauthoridWang, DM=37056806600en_HK
dc.identifier.scopusauthoridYang, DP=22959396400en_HK
dc.identifier.scopusauthoridMo, SL=24921801300en_HK
dc.identifier.scopusauthoridGuan, XY=7201463221en_HK
dc.identifier.scopusauthoridChen, JP=22733695400en_HK
dc.identifier.citeulike9111691-

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