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Reversal of multidrug resistance in cancer cells by pyranocoumarins isolated from Radix Peucedani
Wu J.Y.-C.; Fong W.-F.; Zhang J.-X.; Leung C.-H.; Kwong H.-L.; Yang M.-S.; Li D.; Cheung H.-Y.
2003-07-18
Source PublicationEuropean Journal of Pharmacology
ISSN00142999
Volume473Issue:1Pages:9-17
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 IC 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.
KeywordApoptosis KB-V1 Multidrug resistance P-glycoprotein Peucedanum praeruptorum Dunn Pyranocoumarins
DOI10.1016/S0014-2999(03)01946-0
URLView the original
Language英語
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Cited Times [WOS]:157   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
AffiliationCity University of Hong Kong
Recommended Citation
GB/T 7714
Wu J.Y.-C.,Fong W.-F.,Zhang J.-X.,et al. Reversal of multidrug resistance in cancer cells by pyranocoumarins isolated from Radix Peucedani[J]. European Journal of Pharmacology,2003,473(1):9-17.
APA Wu J.Y.-C..,Fong W.-F..,Zhang J.-X..,Leung C.-H..,Kwong H.-L..,...&Cheung H.-Y..(2003).Reversal of multidrug resistance in cancer cells by pyranocoumarins isolated from Radix Peucedani.European Journal of Pharmacology,473(1),9-17.
MLA Wu J.Y.-C.,et al."Reversal of multidrug resistance in cancer cells by pyranocoumarins isolated from Radix Peucedani".European Journal of Pharmacology 473.1(2003):9-17.
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