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Article: Bioactivity-guided Identification and Cell Signaling Technology to Delineate the Lactate Dehydrogenase a Inhibition Effects of Spatholobus Suberectus on Breast Cancer

TitleBioactivity-guided Identification and Cell Signaling Technology to Delineate the Lactate Dehydrogenase a Inhibition Effects of Spatholobus Suberectus on Breast Cancer
Authors
Issue Date2013
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
PloS One, 2013, v. 8 n. 2, p. e56631 How to Cite?
AbstractAerobic glycolysis is an important feature of cancer cells. In recent years, lactate dehydrogenase A (LDH-A) is emerging as a novel therapeutic target for cancer treatment. Seeking LDH-A inhibitors from natural resources has been paid much attention for drug discovery. Spatholobus suberectus (SS) is a common herbal medicine used in China for treating blood-stasis related diseases such as cancer. This study aims to explore the potential medicinal application of SS for LDH-A inhibition on breast cancer and to determine its bioactive compounds. We found that SS manifested apoptosis-inducing, cell cycle arresting and anti-LDH-A activities in both estrogen-dependent human MCF-7 cells and estrogen-independent MDA-MB-231 cell. Oral herbal extracts (1 g/kg/d) administration attenuated tumor growth and LDH-A expression in both breast cancer xenografts. Bioactivity-guided fractionation finally identified epigallocatechin as a key compound in SS inhibiting LDH-A activity. Further studies revealed that LDH-A plays a critical role in mediating the apoptosis-induction effects of epigallocatechin. The inhibited LDH-A activities by epigallocatechin is attributed to disassociation of Hsp90 from HIF-1alpha and subsequent accelerated HIF-1alpha proteasome degradation. In vivo study also demonstrated that epigallocatechin could significantly inhibit breast cancer growth, HIF-1alpha/LDH-A expression and trigger apoptosis without bringing toxic effects. The preclinical study thus suggests that the potential medicinal application of SS for inhibiting cancer LDH-A activity and the possibility to consider epigallocatechin as a lead compound to develop LDH-A inhibitors. Future studies of SS for chemoprevention or chemosensitization against breast cancer are thus warranted.
Persistent Identifierhttp://hdl.handle.net/10722/195639
ISSN
2015 Impact Factor: 3.057
2015 SCImago Journal Rankings: 1.395
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWang, Z-
dc.contributor.authorWang, D-
dc.contributor.authorHan, S-
dc.contributor.authorWang, N-
dc.contributor.authorMo, F-
dc.contributor.authorLoo, TY-
dc.contributor.authorShen, J-
dc.contributor.authorHuang, H-
dc.contributor.authorChen, J-
dc.date.accessioned2014-03-06T08:17:48Z-
dc.date.available2014-03-06T08:17:48Z-
dc.date.issued2013-
dc.identifier.citationPloS One, 2013, v. 8 n. 2, p. e56631-
dc.identifier.issn1932-6203-
dc.identifier.urihttp://hdl.handle.net/10722/195639-
dc.description.abstractAerobic glycolysis is an important feature of cancer cells. In recent years, lactate dehydrogenase A (LDH-A) is emerging as a novel therapeutic target for cancer treatment. Seeking LDH-A inhibitors from natural resources has been paid much attention for drug discovery. Spatholobus suberectus (SS) is a common herbal medicine used in China for treating blood-stasis related diseases such as cancer. This study aims to explore the potential medicinal application of SS for LDH-A inhibition on breast cancer and to determine its bioactive compounds. We found that SS manifested apoptosis-inducing, cell cycle arresting and anti-LDH-A activities in both estrogen-dependent human MCF-7 cells and estrogen-independent MDA-MB-231 cell. Oral herbal extracts (1 g/kg/d) administration attenuated tumor growth and LDH-A expression in both breast cancer xenografts. Bioactivity-guided fractionation finally identified epigallocatechin as a key compound in SS inhibiting LDH-A activity. Further studies revealed that LDH-A plays a critical role in mediating the apoptosis-induction effects of epigallocatechin. The inhibited LDH-A activities by epigallocatechin is attributed to disassociation of Hsp90 from HIF-1alpha and subsequent accelerated HIF-1alpha proteasome degradation. In vivo study also demonstrated that epigallocatechin could significantly inhibit breast cancer growth, HIF-1alpha/LDH-A expression and trigger apoptosis without bringing toxic effects. The preclinical study thus suggests that the potential medicinal application of SS for inhibiting cancer LDH-A activity and the possibility to consider epigallocatechin as a lead compound to develop LDH-A inhibitors. Future studies of SS for chemoprevention or chemosensitization against breast cancer are thus warranted.-
dc.languageeng-
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action-
dc.relation.ispartofPloS One-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshAntineoplastic Agents - chemistry - pharmacology-
dc.subject.meshBreast Neoplasms - pathology-
dc.subject.meshEnzyme Inhibitors - pharmacology-
dc.subject.meshFabaceae - chemistry-
dc.subject.meshL-Lactate Dehydrogenase - antagonists and inhibitors - genetics-
dc.titleBioactivity-guided Identification and Cell Signaling Technology to Delineate the Lactate Dehydrogenase a Inhibition Effects of Spatholobus Suberectus on Breast Canceren_US
dc.typeArticleen_US
dc.identifier.emailShen, J: shenjg@hkucc.hku.hk-
dc.identifier.emailChen, J: abchen@hku.hk-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0056631-
dc.identifier.pmid23457597-
dc.identifier.pmcidPMC3572989-
dc.identifier.hkuros228222-
dc.identifier.volume8-
dc.identifier.issue2-
dc.identifier.spagee56631-
dc.identifier.epagee56631-
dc.identifier.isiWOS:000315602700087-
dc.publisher.placeUnited States-

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