Laurus nobilis L. Seed Extract Reveals Collateral Sensitivity in Multidrug-Resistant P-Glycoprotein-Expressing Tumor Cells

The frequent failure of standard cancer chemotherapy requires the development of novel drugs capable of killing otherwise drug-resistant tumors. Here, we have investigated a chloroform extract of Laurus nobilis seeds. Fatty acids and 23 constituents of the volatile fraction were identified by gas ch...

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Bibliographic Details
Published in:Nutrition and cancer 2015-05, Vol.67 (4), p.664-675
Main Authors: Saab, Antoine M., Guerrini, Alessandra, Zeino, Maen, Wiench, Benjamin, Rossi, Damiano, Gambari, Roberto, Sacchetti, Gianni, Greten, Henry Johannes, Efferth, Thomas
Format: Article
Language:English
Subjects:
Antineoplastic Agents, Phytogenic - pharmacology
Apoptosis
ATP Binding Cassette Transporter, Sub-Family B - genetics
ATP Binding Cassette Transporter, Sub-Family B - metabolism
Cell Line, Tumor
Cell Survival - drug effects
Chromatography
Doxorubicin - pharmacology
Drug Resistance, Neoplasm
Fatty acids
Flow cytometry
Gas Chromatography-Mass Spectrometry
Glycoproteins
Humans
Laurus - chemistry
Leukemia - pathology
Mass spectrometry
Plant Extracts - pharmacology
Seeds - chemistry
Tumors
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Summary:The frequent failure of standard cancer chemotherapy requires the development of novel drugs capable of killing otherwise drug-resistant tumors. Here, we have investigated a chloroform extract of Laurus nobilis seeds. Fatty acids and 23 constituents of the volatile fraction were identified by gas chromotography/flame ionization detection (GC/FID) and gas chromatography/mass spectrometry (GC/MS), in good agreement with 1 H NMR (nuclear magnetic resonance) spectrum. Multidrug-resistant P-glycoprotein-expressing CEM/ADR5000 leukemia cells were hypersensitive (collaterally sensitive) toward this extract compared to drug-sensitive CCRF-CEM cells, whereas CEM/ADR5000 cells were 2586-fold resistant to doxorubicin as control drug. Collateral sensitivity was verified by measurement of apoptotic cells by flow cytometry. The log 10 IC 50 values of 3 compounds in the extract (limonene, eucalyptol, oleic acid) did not correlate with mRNA expression of the P-glycoprotein-coding ABCB1/MDR1 gene and accumulation of the P-glycoprotein substrate rhodamine in the NCI panel of tumor cell lines. A microarray-based profile of 20 genes predicted resistance to doxorubicin and 7 other anticancer drugs involved in the multidrug resistance phenotype but not to limonene, eucalyptol and oleic acid. In conclusion, our results show that Laurus nobilis seed extract is suitable to kill multidrug-resistant P-glycoprotein expressing tumor cells.
ISSN:0163-5581
1532-7914
DOI:10.1080/01635581.2015.1019632