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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
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
2015 Impact Factor: 2.73
2015 SCImago Journal Rankings: 1.115
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.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

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