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Article: Reversal of multidrug resistance in cancer cells by pyranocoumarins isolated from Radix Peucedani

TitleReversal of multidrug resistance in cancer cells by pyranocoumarins isolated from Radix Peucedani
Authors
KeywordsApoptosis
KB-V1
Multidrug resistance
P-glycoprotein
Peucedanum praeruptorum Dunn
Pyranocoumarins
Issue Date2003
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/ejphar
Citation
European Journal Of Pharmacology, 2003, v. 473 n. 1, p. 9-17 How to Cite?
AbstractThe pyranocoumarins, (±)-3′-angeloyl-4′-acetoxy-cis-khellactone, were isolated from Radix Peucedani, the dry root of Peucedanum praeruptorum Dunn, through bioassay-guided fractionation. The chemical structure of pyranocoumarins was determined by mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy. X-ray crystallography showed that there are eight molecules (i.e. two each of four conformers) in each unit cell with their optical activities equally cancelled out. The four conformers are 3′(R)-angeloyl-4′(R)-acetoxy-khellactone in two conformational forms, and 3′(S)-angeloyl-4′(S)-acetoxy-khellactone in two conformational forms. Pyranocoumarins caused apoptotic cell death with IC50 of 41.9±2.8 and 17.3±8.2 μM for drug-sensitive KB-3-1 and multidrug resistant (MDR) KB-V1, respectively. The two- to threefold sensitivity difference between the two cell lines is interesting considering that the same ratio for doxorubicin is 50-300. Strong synergistic interactions were demonstrated when pyranocoumarins were combined with common anti-tumor drugs including doxorubicin, paclitaxel, puromycin or vincristine in MDR KB-V1 cell line, but not in drug-sensitive KB-3-1 cells. Pyranocoumarins increased doxorubicin accumulation in KB-V1 cells by about 25% after 6 h of incubation. Pyranocoumarins treatment for 24 h down-regulated the expression of P-glycoprotein in KB-V1 cells at both protein and mRNA levels. Pyranocoumarins also transiently reduced the cellular ATP contents in KB-V1 cells in a dose-dependent manner. Our results suggest that pyranocoumarins could be a potential MDR reversing agent. © 2003 Elsevier B.V. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/167794
ISSN
2023 Impact Factor: 4.2
2023 SCImago Journal Rankings: 1.055
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorWu, JYCen_US
dc.contributor.authorFong, WFen_US
dc.contributor.authorZhang, JXen_US
dc.contributor.authorLeung, CHen_US
dc.contributor.authorKwong, HLen_US
dc.contributor.authorYang, MSen_US
dc.contributor.authorLi, Den_US
dc.contributor.authorCheung, HYen_US
dc.date.accessioned2012-10-08T03:11:43Z-
dc.date.available2012-10-08T03:11:43Z-
dc.date.issued2003en_US
dc.identifier.citationEuropean Journal Of Pharmacology, 2003, v. 473 n. 1, p. 9-17en_US
dc.identifier.issn0014-2999en_US
dc.identifier.urihttp://hdl.handle.net/10722/167794-
dc.description.abstractThe pyranocoumarins, (±)-3′-angeloyl-4′-acetoxy-cis-khellactone, were isolated from Radix Peucedani, the dry root of Peucedanum praeruptorum Dunn, through bioassay-guided fractionation. The chemical structure of pyranocoumarins was determined by mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy. X-ray crystallography showed that there are eight molecules (i.e. two each of four conformers) in each unit cell with their optical activities equally cancelled out. The four conformers are 3′(R)-angeloyl-4′(R)-acetoxy-khellactone in two conformational forms, and 3′(S)-angeloyl-4′(S)-acetoxy-khellactone in two conformational forms. Pyranocoumarins caused apoptotic cell death with IC50 of 41.9±2.8 and 17.3±8.2 μM for drug-sensitive KB-3-1 and multidrug resistant (MDR) KB-V1, respectively. The two- to threefold sensitivity difference between the two cell lines is interesting considering that the same ratio for doxorubicin is 50-300. Strong synergistic interactions were demonstrated when pyranocoumarins were combined with common anti-tumor drugs including doxorubicin, paclitaxel, puromycin or vincristine in MDR KB-V1 cell line, but not in drug-sensitive KB-3-1 cells. Pyranocoumarins increased doxorubicin accumulation in KB-V1 cells by about 25% after 6 h of incubation. Pyranocoumarins treatment for 24 h down-regulated the expression of P-glycoprotein in KB-V1 cells at both protein and mRNA levels. Pyranocoumarins also transiently reduced the cellular ATP contents in KB-V1 cells in a dose-dependent manner. Our results suggest that pyranocoumarins could be a potential MDR reversing agent. © 2003 Elsevier B.V. All rights reserved.en_US
dc.languageengen_US
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/ejpharen_US
dc.relation.ispartofEuropean Journal of Pharmacologyen_US
dc.subjectApoptosis-
dc.subjectKB-V1-
dc.subjectMultidrug resistance-
dc.subjectP-glycoprotein-
dc.subjectPeucedanum praeruptorum Dunn-
dc.subjectPyranocoumarins-
dc.subject.meshAdenosine Triphosphate - Metabolismen_US
dc.subject.meshAntineoplastic Agents - Pharmacologyen_US
dc.subject.meshApiaceae - Chemistryen_US
dc.subject.meshBlotting, Westernen_US
dc.subject.meshCell Line, Tumoren_US
dc.subject.meshCrystallography, X-Rayen_US
dc.subject.meshDown-Regulationen_US
dc.subject.meshDrug Resistance, Multiple - Drug Effectsen_US
dc.subject.meshDrug Resistance, Neoplasm - Drug Effectsen_US
dc.subject.meshDrug Synergismen_US
dc.subject.meshHumansen_US
dc.subject.meshMagnetic Resonance Spectroscopyen_US
dc.subject.meshMass Spectrometryen_US
dc.subject.meshP-Glycoprotein - Biosynthesis - Geneticsen_US
dc.subject.meshPlant Extracts - Pharmacologyen_US
dc.subject.meshPlant Roots - Chemistryen_US
dc.subject.meshPlants, Medicinal - Chemistryen_US
dc.subject.meshPyranocoumarins - Pharmacologyen_US
dc.subject.meshRna, Messenger - Biosynthesisen_US
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_US
dc.subject.meshStereoisomerismen_US
dc.titleReversal of multidrug resistance in cancer cells by pyranocoumarins isolated from Radix Peucedanien_US
dc.typeArticleen_US
dc.identifier.emailLeung, CH:duncanl@hkucc.hku.hken_US
dc.identifier.authorityLeung, CH=rp00730en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/S0014-2999(03)01946-0en_US
dc.identifier.pmid12877932-
dc.identifier.scopuseid_2-s2.0-0037810918en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0037810918&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume473en_US
dc.identifier.issue1en_US
dc.identifier.spage9en_US
dc.identifier.epage17en_US
dc.identifier.isiWOS:000184387800002-
dc.publisher.placeNetherlandsen_US
dc.identifier.scopusauthoridWu, JYC=7409255981en_US
dc.identifier.scopusauthoridFong, WF=7102816013en_US
dc.identifier.scopusauthoridZhang, JX=7601354140en_US
dc.identifier.scopusauthoridLeung, CH=7402612570en_US
dc.identifier.scopusauthoridKwong, HL=35571025800en_US
dc.identifier.scopusauthoridYang, MS=7404925734en_US
dc.identifier.scopusauthoridLi, D=26643209100en_US
dc.identifier.scopusauthoridCheung, HY=7201839371en_US
dc.identifier.issnl0014-2999-

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