File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Phloroglucinol derivative MCPP induces cell apoptosis in human colon cancer

TitlePhloroglucinol derivative MCPP induces cell apoptosis in human colon cancer
Authors
Issue Date2011
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/35503
Citation
Journal of Cellular Biochemistry, 2011, v. 112 n. 2, p. 643-652 How to Cite?
Abstract
This study is the first to investigate the anticancer effects of the new phloroglucinol derivative (3,6-bis(3-chlorophenylacetyl)phloroglucinol; MCPP) in human colon cancer cells. MCPP induced cell death and antiproliferation in three human colon cancer, HCT-116, SW480, and Caco-2 cells, but not in primary human dermal fibroblast cells. MCPP-induced concentration-dependent apoptotic cell death in colon cancer cells was measured by fluorescence-activated cell sorter (FACS) analysis. Treatment of HCT-116 human colon cancer cells with MCPP was found to induce a number of signature endoplasmic reticulum (ER) stress markers; and up-regulation of CCAAT/enhancer-binding protein homologous protein (CHOP) and glucose-regulated protein (GRP)-78, phosphorylation of eukaryotic initiation factor-2alpha (eIF-2alpha), suggesting the induction of ER stress. MCPP also increased GSK3alpha/beta(Tyr270/216) phosphorylation and reduced GSK3alpha/beta(Ser21/9) phosphorylation time-dependently. Transfection of cells with GRP78 or CHOP siRNA, or treatment of GSK3 inhibitor SB216163 reduced MCPP-mediated cell apoptosis. Treatment of MCPP also increased caspase-7, caspase-9, and caspase-3 activity. The inhibition of caspase activity by z-DEVE-FMK or z-VAD-FMK significantly reduced MCPP-induced apoptosis. Furthermore, treatment of GSK3 inhibitor SB216763 also dramatically reversed MCPP-induced GRP and CHOP up-regulation, and pro-caspase-3 and pro-caspase-9 degradation. Taken together, the present study provides evidences to support that GRP78 and CHOP expression, and GSK3alpha/beta activation in mediating the MCPP-induced human colon cancer cell apoptosis. © 2010 Wiley-Liss, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/138935
ISSN
2013 Impact Factor: 3.368
ISI Accession Number ID
Funding AgencyGrant Number
National Science Council98-2320-B-039-009-MY2
98-2627-B-039-005
China Medical University HospitalDMR-99-152
Funding Information:

Grant sponsor: National Science Council; Grant numbers: 98-2320-B-039-009-MY2, 98-2627-B-039-005; Grant sponsor: China Medical University Hospital; Grant number: DMR-99-152.

References

 

Author Affiliations
  1. The University of Hong Kong Li Ka Shing Faculty of Medicine
  2. null
  3. China Medical University Hospital Taichung
  4. Buddhist Tzu-Chi General Hospital Taiwan
DC FieldValueLanguage
dc.contributor.authorHuang, SMen_US
dc.contributor.authorCheung, CWen_US
dc.contributor.authorChang, CSen_US
dc.contributor.authorTang, CHen_US
dc.contributor.authorLiu, JFen_US
dc.contributor.authorLin, YHen_US
dc.contributor.authorChen, JHen_US
dc.contributor.authorKo, SHen_US
dc.contributor.authorWong, KLen_US
dc.contributor.authorLu, DYen_US
dc.date.accessioned2011-09-23T05:42:19Z-
dc.date.available2011-09-23T05:42:19Z-
dc.date.issued2011en_US
dc.identifier.citationJournal of Cellular Biochemistry, 2011, v. 112 n. 2, p. 643-652en_US
dc.identifier.issn0730-2312-
dc.identifier.urihttp://hdl.handle.net/10722/138935-
dc.description.abstractThis study is the first to investigate the anticancer effects of the new phloroglucinol derivative (3,6-bis(3-chlorophenylacetyl)phloroglucinol; MCPP) in human colon cancer cells. MCPP induced cell death and antiproliferation in three human colon cancer, HCT-116, SW480, and Caco-2 cells, but not in primary human dermal fibroblast cells. MCPP-induced concentration-dependent apoptotic cell death in colon cancer cells was measured by fluorescence-activated cell sorter (FACS) analysis. Treatment of HCT-116 human colon cancer cells with MCPP was found to induce a number of signature endoplasmic reticulum (ER) stress markers; and up-regulation of CCAAT/enhancer-binding protein homologous protein (CHOP) and glucose-regulated protein (GRP)-78, phosphorylation of eukaryotic initiation factor-2alpha (eIF-2alpha), suggesting the induction of ER stress. MCPP also increased GSK3alpha/beta(Tyr270/216) phosphorylation and reduced GSK3alpha/beta(Ser21/9) phosphorylation time-dependently. Transfection of cells with GRP78 or CHOP siRNA, or treatment of GSK3 inhibitor SB216163 reduced MCPP-mediated cell apoptosis. Treatment of MCPP also increased caspase-7, caspase-9, and caspase-3 activity. The inhibition of caspase activity by z-DEVE-FMK or z-VAD-FMK significantly reduced MCPP-induced apoptosis. Furthermore, treatment of GSK3 inhibitor SB216763 also dramatically reversed MCPP-induced GRP and CHOP up-regulation, and pro-caspase-3 and pro-caspase-9 degradation. Taken together, the present study provides evidences to support that GRP78 and CHOP expression, and GSK3alpha/beta activation in mediating the MCPP-induced human colon cancer cell apoptosis. © 2010 Wiley-Liss, Inc.-
dc.languageengen_US
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/35503-
dc.relation.ispartofJournal of Cellular Biochemistryen_US
dc.rightsJournal of Cellular Biochemistry. Copyright © John Wiley & Sons, Inc.-
dc.subject.meshCell Line, Tumor-
dc.subject.meshColonic Neoplasms - genetics - metabolism-
dc.subject.meshMediator Complex - genetics-
dc.subject.meshPhloroglucinol - analogs and derivatives - pharmacology-
dc.subject.meshTranscription Factor CHOP/genetics-
dc.titlePhloroglucinol derivative MCPP induces cell apoptosis in human colon canceren_US
dc.typeArticleen_US
dc.identifier.emailCheung, CW: cheucw@hku.hken_US
dc.identifier.emailWong, KL: wongeric@hku.hken_US
dc.identifier.authorityCheung, CW=rp00244en_US
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/jcb.22966-
dc.identifier.pmid21268086-
dc.identifier.scopuseid_2-s2.0-79251629978-
dc.identifier.hkuros193530en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79251629978&selection=ref&src=s&origin=recordpage-
dc.identifier.volume112en_US
dc.identifier.issue2en_US
dc.identifier.spage643en_US
dc.identifier.epage652en_US
dc.identifier.isiWOS:000287071900033-
dc.publisher.placeUnited States-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats