A flavone and cytotoxic activity of sesquiterpenoids from the resinous exudates of cushion bush (Leucophyta brownii)

KT Jensen; MG Hyldgaard; S Purup; X Fretté; LP Christensen

doi:10.1055/s-0036-1596759

Planta Medica, Table of Contents

Planta Med 2016; 82(S 01): S1-S381
DOI: 10.1055/s-0036-1596759

Abstracts

Georg Thieme Verlag KG Stuttgart · New York

A flavone and cytotoxic activity of sesquiterpenoids from the resinous exudates of cushion bush (Leucophyta brownii)

Authors

KT Jensen

¹Department of Chemical Engineering, Biotechnology and Environmental Technology, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark
MG Hyldgaard

¹Department of Chemical Engineering, Biotechnology and Environmental Technology, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark
S Purup

²Department of Animal Science, Aarhus University, Blichers Allé 20, 8830 Tjele, Denmark
X Fretté

¹Department of Chemical Engineering, Biotechnology and Environmental Technology, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark
LP Christensen

¹Department of Chemical Engineering, Biotechnology and Environmental Technology, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark

Abstract

Full Text

A reinvestigation of the resinous exudates of cushion bush (Leucophyta brownii Cass., Asteraceae) resulted in the isolation of the 8,12-guaianolides 1-4, the xanthanolide tomentosin (5), and the 1,10-seco-eudesmane leucophytalin C (6) previously isolated from this plant [1], as well as the flavone 7,4'-dihydroxy-5,8-dimethoxyflavone (7). The flavone 7 has previously been synthesized [2] but to the best of our knowledge this is its first report from natural sources. The flavone 7 was identified by 1D and 2D NMR techniques, UV and LC-MS/MS. Sesquiterpene lactones containing an α,β-unsaturated γ-lactone moiety are known for their anti-inflammatory and cytotoxic activity due to reactions with sulfhydryl groups of functional proteins via a Michael-type reaction [1]. Compounds 1-6 were investigated for their cytotoxic activity towards human breast cancer (MCF-7) and colon cancer (HT-29) cells and their ability to induce apoptosis. Compounds 1-4 reduced proliferation of HT-29 and MCF-7 cells between 60 – 90% at a concentration of 18.9, 16.3, 20.2 and 17.2µM, respectively, and with IC₅₀ values < 10µM. Tomentosin (5) showed less cytotoxicity with an IC₅₀ value of approximately 40µM for both cell lines. As expected leucophytalin C (6) with the absence of an α,β-unsaturated γ-lactone moiety did not show any significant cytotoxicity at a concentration of 79.4µM. No activation of caspase-3, -7 and -8 were observed in the tested cancer cell lines. This was also confirmed by gene expression studies, indicating that the observed cytotoxic effect of compounds 1-5 was not due to an apoptosis initiated mechanism.

Acknowledgements: A. K. Nielsen and K. B. Poulsen are acknowledged for technical assistance.

Keywords: Leucophyta brownii, 7,4'-dihydroxy-5,8-dimethoxyflavone, 8,12-guaianolides, cytotoxicity, apoptosis.

References:

[1] Hyldgaard MG, Purup S, Bond AD, Fretté XC, Qu H, Jensen KT, Christensen LP. Guaianolides and a seco-eudesmane from the resinous exudates of cushion bush (Leucophyta brownii) and evaluation of their cytostatic and anti-inflammatory activity. J Nat Prod 2015; 78: 1877 – 1885

[2] Gupta SR, Seshadri TR, Sharma CS, Sharma ND. Chemical investigation of Dikamali gum: isolation of a new flavone, 4'-hydroxywogonin. Indian J Chem 1975; 13: 785 – 788

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