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Article: Induction of apoptosis in K562 cells by dicyclohexylammonium salt of hyperforin through a mitochondrial-related pathway

TitleInduction of apoptosis in K562 cells by dicyclohexylammonium salt of hyperforin through a mitochondrial-related pathway
Authors
KeywordsAntitumor activity
Apoptosis
Hyperforin derivatives
K562 cells
Issue Date2011
PublisherElsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/chembioint
Citation
Chemico-Biological Interactions, 2011, v. 190 n. 2-3, p. 91-101 How to Cite?
AbstractHyperforin is an abundant phloroglucinol-type constituent isolated from the extract of the flowering upper portion of the plant Hypericum perforatum L. The dicyclohexylammonium salt of hyperforin (DCHA-HF) has exhibited antitumor and antiangiogenic activities in various cancer cells. Here, the antitumor effects of DCHA-HF on the chronic myeloid leukemia K562 cell line were investigated for the first time. DCHA-HF exhibited dose- and time-dependent inhibitory activities against K562 cells, with IC 50 values of 8.6 and 3.2 μM for 48 h and 72 h of treatment, respectively, which was more effective than that of the hyperforin. In contrast, little cytotoxic activity was observed with DCHA-HF on HUVECs. DCHA-HF treatment resulted in induction of apoptosis as evidenced from DNA fragmentation, nuclear condensation and increase of early apoptotic cells by DAPI staining analysis, TUNEL assay and Annexin V-FITC/PI double-labeled staining analysis, respectively. Moreover, DCHA-HF elicited dissipation of mitochondrial transmembrane potential that commenced with the release of cytochrome c through down-regulation of expression of anti-apoptotic proteins and up-regulation of expression of pro-apoptotic proteins. DCHA-HF treatment induced activation of the caspase 3, 8, and 9 cascade and subsequent PARP cleavage, and DCHA-HF-induced apoptosis was significantly inhibited by caspase inhibitors. Treated cells were arrested at the G1 phase of the cell cycle and the expression of p53 and p27 Kip1, two key regulators related to cell cycle and apoptosis, was up-regulated. These results suggest that DCHA-HF inhibits K562 cell growth by inducing caspase-dependent apoptosis mediated by a mitochondrial pathway and arresting the cell cycle at the G1 phase. Therefore, DCHA-HF is a potential chemotherapeutic antitumor drug for chronic myeloid leukemia therapy. © 2011 Elsevier Ireland Ltd. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/138120
ISSN
2015 Impact Factor: 2.618
2015 SCImago Journal Rankings: 1.072
ISI Accession Number ID
Funding AgencyGrant Number
International Science & Technology Cooperation Program of China2009DFA31230
International Science & Technology Cooperation Program of Guangdong Province, China20090501
National Natural Science Foundation of China81001449
Fundamental Research Funds for the Central Universities21609303
Funding Information:

This work was supported by grants from the International Science & Technology Cooperation Program of China (2009DFA31230), the International Science & Technology Cooperation Program of Guangdong Province, China (20090501), the National Natural Science Foundation of China (81001449), and the Fundamental Research Funds for the Central Universities (21609303).

References

 

DC FieldValueLanguage
dc.contributor.authorLiu, JYen_HK
dc.contributor.authorLiu, Zen_HK
dc.contributor.authorWang, DMen_HK
dc.contributor.authorLi, MMen_HK
dc.contributor.authorWang, SXen_HK
dc.contributor.authorWang, Ren_HK
dc.contributor.authorChen, JPen_HK
dc.contributor.authorWang, YFen_HK
dc.contributor.authorYang, DPen_HK
dc.date.accessioned2011-08-26T14:41:02Z-
dc.date.available2011-08-26T14:41:02Z-
dc.date.issued2011en_HK
dc.identifier.citationChemico-Biological Interactions, 2011, v. 190 n. 2-3, p. 91-101en_HK
dc.identifier.issn0009-2797en_HK
dc.identifier.urihttp://hdl.handle.net/10722/138120-
dc.description.abstractHyperforin is an abundant phloroglucinol-type constituent isolated from the extract of the flowering upper portion of the plant Hypericum perforatum L. The dicyclohexylammonium salt of hyperforin (DCHA-HF) has exhibited antitumor and antiangiogenic activities in various cancer cells. Here, the antitumor effects of DCHA-HF on the chronic myeloid leukemia K562 cell line were investigated for the first time. DCHA-HF exhibited dose- and time-dependent inhibitory activities against K562 cells, with IC 50 values of 8.6 and 3.2 μM for 48 h and 72 h of treatment, respectively, which was more effective than that of the hyperforin. In contrast, little cytotoxic activity was observed with DCHA-HF on HUVECs. DCHA-HF treatment resulted in induction of apoptosis as evidenced from DNA fragmentation, nuclear condensation and increase of early apoptotic cells by DAPI staining analysis, TUNEL assay and Annexin V-FITC/PI double-labeled staining analysis, respectively. Moreover, DCHA-HF elicited dissipation of mitochondrial transmembrane potential that commenced with the release of cytochrome c through down-regulation of expression of anti-apoptotic proteins and up-regulation of expression of pro-apoptotic proteins. DCHA-HF treatment induced activation of the caspase 3, 8, and 9 cascade and subsequent PARP cleavage, and DCHA-HF-induced apoptosis was significantly inhibited by caspase inhibitors. Treated cells were arrested at the G1 phase of the cell cycle and the expression of p53 and p27 Kip1, two key regulators related to cell cycle and apoptosis, was up-regulated. These results suggest that DCHA-HF inhibits K562 cell growth by inducing caspase-dependent apoptosis mediated by a mitochondrial pathway and arresting the cell cycle at the G1 phase. Therefore, DCHA-HF is a potential chemotherapeutic antitumor drug for chronic myeloid leukemia therapy. © 2011 Elsevier Ireland Ltd. All rights reserved.en_HK
dc.languageengen_US
dc.publisherElsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/chembiointen_HK
dc.relation.ispartofChemico-Biological Interactionsen_HK
dc.subjectAntitumor activityen_HK
dc.subjectApoptosisen_HK
dc.subjectHyperforin derivativesen_HK
dc.subjectK562 cellsen_HK
dc.subject.meshAntineoplastic Agents - chemistry - toxicity-
dc.subject.meshApoptosis-
dc.subject.meshHypericum - chemistry-
dc.subject.meshMitochondria - drug effects - metabolism-
dc.subject.meshTerpenes - chemistry - toxicity-
dc.titleInduction of apoptosis in K562 cells by dicyclohexylammonium salt of hyperforin through a mitochondrial-related pathwayen_HK
dc.typeArticleen_HK
dc.identifier.emailChen, JP: abchen@hku.hken_HK
dc.identifier.authorityChen, JP=rp01316en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.cbi.2011.02.026en_HK
dc.identifier.pmid21376709-
dc.identifier.scopuseid_2-s2.0-79955474334en_HK
dc.identifier.hkuros189749en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79955474334&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume190en_HK
dc.identifier.issue2-3en_HK
dc.identifier.spage91en_HK
dc.identifier.epage101en_HK
dc.identifier.isiWOS:000291119800004-
dc.publisher.placeIrelanden_HK
dc.identifier.scopusauthoridLiu, JY=37665485000en_HK
dc.identifier.scopusauthoridLiu, Z=36458787200en_HK
dc.identifier.scopusauthoridWang, DM=36955783900en_HK
dc.identifier.scopusauthoridLi, MM=15848754300en_HK
dc.identifier.scopusauthoridWang, SX=36982394500en_HK
dc.identifier.scopusauthoridWang, R=36716793800en_HK
dc.identifier.scopusauthoridChen, JP=22733695400en_HK
dc.identifier.scopusauthoridWang, YF=35277747300en_HK
dc.identifier.scopusauthoridYang, DP=22959396400en_HK
dc.identifier.citeulike8960873-

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