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Article: Herbal diterpenoids induce growth arrest and apoptosis in colon cancer cells with increased expression of the nonsteroidal anti-inflammatory drug-activated gene

TitleHerbal diterpenoids induce growth arrest and apoptosis in colon cancer cells with increased expression of the nonsteroidal anti-inflammatory drug-activated gene
Authors
KeywordsApoptosis
Colon cancer
Growth arrest
NAG-1
Pseudolaric acid B
Triptolide
Issue Date2007
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/ejphar
Citation
European Journal Of Pharmacology, 2007, v. 559 n. 1, p. 1-13 How to Cite?
AbstractNovel chemotherapeutic agents derived from active phytochemicals could be used as adjuvants and improve the anti-carcinogenicity of standard drug treatments. However, their precise mechanisms of action are sometimes unclear. In this study, the anti-carcinogenic effect of the herbal diterpenoid pseudolaric acid B (PAB) on the growth and apoptosis of colon cancer cells was investigated, and to compare that with the more toxic compound triptolide. PAB induced growth inhibition and apoptosis in HT-29 cells, which were associated with cell cycle arrest at the G2/M phase, modulation of cyclin expression and downregulation of the protooncogene c-myc. In addition, PAB also inhibited bcl-xL expression, induced cleavage of procaspase-3 and its substrate poly(ADP-ribose) polymerase (PARP), which together caused DNA fragmentation and nuclear chromatin condensation. Concomitantly, the modulation of the growth-related and apoptotic factors by PAB was accompanied by the increased protein and gene expression of the nonsteroidal anti-inflammatory drug-activated gene (NAG-1), which occurred along with cyclooxygenase-2 inhibition. The effects of PAB on PARP cleavage and NAG-1 overexpression were not reversible upon removal of the drug from the culture medium. Similar cytotoxic and pro-apoptotic effects were also attained by treating the HT-29 cells with another diterpenoid triptolide, but its actions on cell cycle progression and on the upstream transcriptional regulation of NAG-1 both took place in a less coherent manner. These findings exemplify the potential of herbal terpenoids, particularly PAB, in modulating colon cancer carcinogenesis through known molecular targets and precise mechanism of action. © 2007 Elsevier B.V. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/70190
ISSN
2015 Impact Factor: 2.73
2015 SCImago Journal Rankings: 1.115
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorKo, JKSen_HK
dc.contributor.authorLeung, WCen_HK
dc.contributor.authorHo, WKen_HK
dc.contributor.authorChiu, Pen_HK
dc.date.accessioned2010-09-06T06:20:34Z-
dc.date.available2010-09-06T06:20:34Z-
dc.date.issued2007en_HK
dc.identifier.citationEuropean Journal Of Pharmacology, 2007, v. 559 n. 1, p. 1-13en_HK
dc.identifier.issn0014-2999en_HK
dc.identifier.urihttp://hdl.handle.net/10722/70190-
dc.description.abstractNovel chemotherapeutic agents derived from active phytochemicals could be used as adjuvants and improve the anti-carcinogenicity of standard drug treatments. However, their precise mechanisms of action are sometimes unclear. In this study, the anti-carcinogenic effect of the herbal diterpenoid pseudolaric acid B (PAB) on the growth and apoptosis of colon cancer cells was investigated, and to compare that with the more toxic compound triptolide. PAB induced growth inhibition and apoptosis in HT-29 cells, which were associated with cell cycle arrest at the G2/M phase, modulation of cyclin expression and downregulation of the protooncogene c-myc. In addition, PAB also inhibited bcl-xL expression, induced cleavage of procaspase-3 and its substrate poly(ADP-ribose) polymerase (PARP), which together caused DNA fragmentation and nuclear chromatin condensation. Concomitantly, the modulation of the growth-related and apoptotic factors by PAB was accompanied by the increased protein and gene expression of the nonsteroidal anti-inflammatory drug-activated gene (NAG-1), which occurred along with cyclooxygenase-2 inhibition. The effects of PAB on PARP cleavage and NAG-1 overexpression were not reversible upon removal of the drug from the culture medium. Similar cytotoxic and pro-apoptotic effects were also attained by treating the HT-29 cells with another diterpenoid triptolide, but its actions on cell cycle progression and on the upstream transcriptional regulation of NAG-1 both took place in a less coherent manner. These findings exemplify the potential of herbal terpenoids, particularly PAB, in modulating colon cancer carcinogenesis through known molecular targets and precise mechanism of action. © 2007 Elsevier B.V. All rights reserved.en_HK
dc.languageengen_HK
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/ejpharen_HK
dc.relation.ispartofEuropean Journal of Pharmacologyen_HK
dc.rightsEuropean Journal of Pharmacology . Copyright © Elsevier BV.en_HK
dc.subjectApoptosisen_HK
dc.subjectColon canceren_HK
dc.subjectGrowth arresten_HK
dc.subjectNAG-1en_HK
dc.subjectPseudolaric acid Ben_HK
dc.subjectTriptolideen_HK
dc.titleHerbal diterpenoids induce growth arrest and apoptosis in colon cancer cells with increased expression of the nonsteroidal anti-inflammatory drug-activated geneen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0014-2999&volume=559&spage=1&epage=13&date=2006&atitle=Herbal+Diterpenoids+Induce+Growth+Arrest+and+Apoptosis+in+Colon+Cancer+Cells+with+Increased+Expression+of+the+Nonsteroidal+Anti-inflammatory+Drug-activated+Gene+en_HK
dc.identifier.emailChiu, P:pchiu@hku.hken_HK
dc.identifier.authorityChiu, P=rp00680en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.ejphar.2006.12.004en_HK
dc.identifier.pmid17258704-
dc.identifier.scopuseid_2-s2.0-33847069296en_HK
dc.identifier.hkuros131598en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33847069296&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume559en_HK
dc.identifier.issue1en_HK
dc.identifier.spage1en_HK
dc.identifier.epage13en_HK
dc.identifier.isiWOS:000244968500001-
dc.publisher.placeNetherlandsen_HK
dc.identifier.scopusauthoridKo, JKS=7402678571en_HK
dc.identifier.scopusauthoridLeung, WC=15849155900en_HK
dc.identifier.scopusauthoridHo, WK=36855638000en_HK
dc.identifier.scopusauthoridChiu, P=11140148700en_HK

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