title: Laurus nobilis L. Seed Extract Reveals Collateral Sensitivity in Multidrug-Resistant P-Glycoprotein-Expressing Tumor Cells.
abstract: 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 log10IC50 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.
authors.affiliation: a Faculty of Sciences II , Lebanese University , Chemistry Department , Beirut , Lebanon.
authors.forename: Antoine M
authors.initials: AM
authors.lastname: Saab
authors.forename: Alessandra
authors.initials: A
authors.lastname: Guerrini
authors.forename: Maen
authors.initials: M
authors.lastname: Zeino
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wiench
authors.forename: Damiano
authors.initials: D
authors.lastname: Rossi
authors.forename: Roberto
authors.initials: R
authors.lastname: Gambari
authors.forename: Gianni
authors.initials: G
authors.lastname: Sacchetti
authors.forename: Henry Johannes
authors.initials: HJ
authors.lastname: Greten
authors.forename: Thomas
authors.initials: T
authors.lastname: Efferth
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D027442:Laurus / Q000737:chemistry*; D007938:Leukemia / Q000473:pathology; D010936:Plant Extracts / Q000494:pharmacology*; D012639:Seeds / Q000737:chemistry*
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D004317:Doxorubicin