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Article: The novel phloroglucinol derivative BFP induces apoptosis of glioma cancer through reactive oxygen species and endoplasmic reticulum stress pathways

TitleThe novel phloroglucinol derivative BFP induces apoptosis of glioma cancer through reactive oxygen species and endoplasmic reticulum stress pathways
Authors
KeywordsPrenyl-phloroglucinol derivatives
ROS
Apoptosis
Glioma
ER stress
Issue Date2012
PublisherElsevier GmbH - Urban und Fischer Verlag. The Journal's web site is located at http://www.elsevier.com/locate/phytomed
Citation
Phytomedicine, 2012, v. 19 n. 12, p. 1093-1100 How to Cite?
AbstractPrenyl-phloroglucinol derivatives from hop plants have been shown to have anticancer activities. This study is the first to investigate the anticancer effects of the new phloroglucinol derivative (2,4-bis(4-fluorophenylacetyl)phloroglucinol; BFP). BFP induced cell death and anti-proliferation in three glioma, U251, U87 and C6 cells, but not in primary human astrocytes. BFP-induced concentration-dependently cell death in glioma cells was determined by MTT and SRB assay. Moreover, BFP-induced apoptotic cell death in glioma cells was measured by Hochest 33258 staining and fluorescence-activated cell sorter (FACS) of propidine iodine (PI) analysis. Treatment of U251 human glioma cells with BFP was also found to induce reactive oxygen species (ROS) generation, which was detected by a fluorescence dye used FACS analysis. Treatment of BFP also increased a number of signature endoplasmic reticulum (ER) stress markers glucose-regulated protein (GRP)-78, GRP-94, IRE1, phosphorylation of eukaryotic initiation factor-2α (eIF-2α) and up-regulation of CAAT/enhancer-binding protein homologous protein (CHOP). Moreover, treatment of BFP also increased the down-stream caspase activation, such as pro-caspase-7 and pro-caspase-12 degradation, suggesting the induction of ER stress. Furthermore, BFP also induced caspase-9 and caspase-3 activation as well as up-regulation of cleaved PARP expression. Treatment of antioxidants, or pre-transfection of cells with GRP78 or CHOP siRNA reduced BFP-mediated apoptotic-related protein expression. Taken together, the present study provides evidences to support that ROS generation, GRP78 and CHOP activation are mediating the BFP-induced human glioma cell apoptosis.
Persistent Identifierhttp://hdl.handle.net/10722/159252
ISSN
2017 Impact Factor: 3.61
2015 SCImago Journal Rankings: 1.013
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLu, DY-
dc.contributor.authorChang, CS-
dc.contributor.authorYeh, WL-
dc.contributor.authorTang, CH-
dc.contributor.authorCheung, CW-
dc.contributor.authorLeung, YM-
dc.contributor.authorLiu, JF-
dc.contributor.authorWong, K-
dc.date.accessioned2012-08-16T05:47:12Z-
dc.date.available2012-08-16T05:47:12Z-
dc.date.issued2012-
dc.identifier.citationPhytomedicine, 2012, v. 19 n. 12, p. 1093-1100-
dc.identifier.issn0944-7113-
dc.identifier.urihttp://hdl.handle.net/10722/159252-
dc.description.abstractPrenyl-phloroglucinol derivatives from hop plants have been shown to have anticancer activities. This study is the first to investigate the anticancer effects of the new phloroglucinol derivative (2,4-bis(4-fluorophenylacetyl)phloroglucinol; BFP). BFP induced cell death and anti-proliferation in three glioma, U251, U87 and C6 cells, but not in primary human astrocytes. BFP-induced concentration-dependently cell death in glioma cells was determined by MTT and SRB assay. Moreover, BFP-induced apoptotic cell death in glioma cells was measured by Hochest 33258 staining and fluorescence-activated cell sorter (FACS) of propidine iodine (PI) analysis. Treatment of U251 human glioma cells with BFP was also found to induce reactive oxygen species (ROS) generation, which was detected by a fluorescence dye used FACS analysis. Treatment of BFP also increased a number of signature endoplasmic reticulum (ER) stress markers glucose-regulated protein (GRP)-78, GRP-94, IRE1, phosphorylation of eukaryotic initiation factor-2α (eIF-2α) and up-regulation of CAAT/enhancer-binding protein homologous protein (CHOP). Moreover, treatment of BFP also increased the down-stream caspase activation, such as pro-caspase-7 and pro-caspase-12 degradation, suggesting the induction of ER stress. Furthermore, BFP also induced caspase-9 and caspase-3 activation as well as up-regulation of cleaved PARP expression. Treatment of antioxidants, or pre-transfection of cells with GRP78 or CHOP siRNA reduced BFP-mediated apoptotic-related protein expression. Taken together, the present study provides evidences to support that ROS generation, GRP78 and CHOP activation are mediating the BFP-induced human glioma cell apoptosis.-
dc.languageeng-
dc.publisherElsevier GmbH - Urban und Fischer Verlag. The Journal's web site is located at http://www.elsevier.com/locate/phytomed-
dc.relation.ispartofPhytomedicine-
dc.subjectPrenyl-phloroglucinol derivatives-
dc.subjectROS-
dc.subjectApoptosis-
dc.subjectGlioma-
dc.subjectER stress-
dc.titleThe novel phloroglucinol derivative BFP induces apoptosis of glioma cancer through reactive oxygen species and endoplasmic reticulum stress pathways-
dc.typeArticle-
dc.identifier.emailCheung, CW: cheucw@hku.hk-
dc.identifier.emailWong, K: wongeric@hku.hk-
dc.identifier.authorityCheung, CW=rp00244-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.phymed.2012.06.010-
dc.identifier.pmid22819448-
dc.identifier.scopuseid_2-s2.0-84866415246-
dc.identifier.hkuros204269-
dc.identifier.hkuros204278-
dc.identifier.volume19-
dc.identifier.issue12-
dc.identifier.spage1093-
dc.identifier.epage1100-
dc.identifier.isiWOS:000311129000007-
dc.publisher.placeGermany-

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