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Gene expression signature-based chemcial genomics and activity pattern in a panel of tumour cell lines propose linalyl acetate as a protein kinase/NF-κB inhibitor
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology. (Cancer Pharmacology and Informatics)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology. (Cancer Pharmacology and Informatics)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology. (Cancer Pharmacology and Informatics)
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2008 (English)In: Gene Therapy and Molecular Biology, ISSN 1529-9120, Vol. 12, no B, 359-370 p.Article in journal (Refereed) Published
Abstract [en]

The essential oil of Lebanese sage, Salvia libanotica, was reported to have anti-tumour activity; however, the mechanism of action has not been identified yet. In this study, 14- cancer cell lines including drug-sensitive and resistant lung, leukaemia, and colon, as well as primary human tumours of chronic lymphocytic leukaemia (CLL) and primary normal mononuclear cells (PBMCs) were used to characterize the anti-tumour activity and mechanism of action of linalyl acetate, a component of the Lebanese sage essential oil. Drug activity and gene expression data sets were utilized to identify drugs with similar activity patterns and genes involved in drug sensitivity/resistance. In addition, the Connectivity Map, a gene expression signature-based screening approach, assisted in predicting further the molecular action of linalyl acetate. Small cell lung carcinoma and colorectal cancer cell lines were the most sensitive to the drug and greater tumour selectivity was observed against chronic lymphocytic leukaemia cells compared to normal mononuclear cells. Only limited effect of some of the classical mechanisms of multi-drug resistance on the activity of Linalyl acetate was noted which makes it potentially interesting for drug-resistant patients. There was high similarity between the activity-pattern/gene expression profile of linalyl acetate and that of protein kinase/NF-kappa B inhibitors. Validating this, linalyl acetate was found to strongly inhibit Janus kinase, JAK3, and p38 alpha kinases in a cell-free assay as well as the NF-kappa B translocation in a dose-dependent manner. Taken together, our results show that the NF-kappa B inhibitor, linalyl acetate, may represent a new therapeutic compound in the management of inflammation and cancer.

Place, publisher, year, edition, pages
2008. Vol. 12, no B, 359-370 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-103309ISI: 000265623400018OAI: oai:DiVA.org:uu-103309DiVA: diva2:218036
Available from: 2009-05-18 Created: 2009-05-18 Last updated: 2015-02-11

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http://www.gtmb.org/pages/vol12B/PDF/33._Hassan_et_al,_359-370.pdf

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Göransson, HannaIsaksson, AndersLarsson, Rolf

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