Planta Med 2017; 83(06): 574-581
DOI: 10.1055/s-0042-118650
Natural Product Chemistry and Analytical Studies
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Investigation of the Lignan Content in Extracts from Linum, Callitris and Juniperus Species in Relation to Their In Vitro Antiproliferative Activities

Joël Doussot*
1   LBLGC, Université dʼOrléans, Orléans, France
2   Ecole SITI (Département CASER), Conservatoire National des Arts et Métiers, Paris, France
,
Véronique Mathieu*
3   Faculté de Pharmacie, Laboratoire de Cancérologie et de Toxicologie Expérimentale, Université Libre de Bruxelles, Brussels, Belgium
,
Cyril Colas
4   Plate-forme HRMS Spectrométrie de Masse Haute Résolution, Fédération de Recherche Physique et Chimie du Vivant, Université dʼOrléans, Orléans, France
,
Roland Molinié
5   Biologie des Plantes et Innovation, Université de Picardie Jules Verne, Amiens, France
,
Cyrielle Corbin
1   LBLGC, Université dʼOrléans, Orléans, France
,
Josiane Montguillon
1   LBLGC, Université dʼOrléans, Orléans, France
,
Laeticia Moreno Y Banuls
3   Faculté de Pharmacie, Laboratoire de Cancérologie et de Toxicologie Expérimentale, Université Libre de Bruxelles, Brussels, Belgium
,
Sullivan Renouard
1   LBLGC, Université dʼOrléans, Orléans, France
,
Frédéric Lamblin
1   LBLGC, Université dʼOrléans, Orléans, France
,
Patricia Dupré
6   Centro de Investigacion y Asistencia en Tecnología y Diseno del Estado de Jalisco, Guadalajara, Mexico
,
Benoit Maunit
7   Institut de Chimie Organique et Analytique, Université dʼOrléans, Orléans, France
,
Robert Kiss
3   Faculté de Pharmacie, Laboratoire de Cancérologie et de Toxicologie Expérimentale, Université Libre de Bruxelles, Brussels, Belgium
,
Christophe Hano
1   LBLGC, Université dʼOrléans, Orléans, France
,
Eric Lainé
1   LBLGC, Université dʼOrléans, Orléans, France
› Author Affiliations
Further Information

Publication History

received 22 April 2016
revised 05 September 2016

accepted 29 September 2016

Publication Date:
24 October 2016 (online)

Abstract

Podophyllotoxin, a lignan still extracted from the rhizomes of Podophyllum hexandrum (Berberidaceae), is the starting molecule for the semisynthesis of widely used anticancer drugs such as etoposide. However, this source is threatened by the over-collection of P. hexandrum. Plants belonging to the Linaceae and Cupressaceae families could be attractive alternative sources with species that contain the lignan podophyllotoxin or its precursors and derivatives. Wild flax species, such as Linum flavum, as well as some Juniperus and Callitris species were investigated for their lignan content, and the in vitro antiproliferative capacity of their extracts was assayed on four tumor cell lines. Some of the lignans were detected by LC-HRMS for the first time in these extracts.

In addition, lignans purified from these plants and compounds semisynthesized from commercially available podophyllotoxin were tested in terms of their in vitro antiproliferative activity. The genus Juniperus was the most promising given its in vitro antiproliferative effects, which were also observed with extracts from L. flavum and Callitris species.

The in vitro antiproliferative effect of the plant extracts studied here appears to correlate well with the contents of the aryltetralin lignan podophyllotoxin and its glycoside as well as with deoxypodophyllotoxin and 6-methoxypodophyllotoxin. The strongest correlation between the lignan content of the extracts and the antiproliferative activity was observed for 6-methoxypodophyllotoxin. Regarding the possibility of producing large renewable amounts of 6-methoxypodophyllotoxin, this molecule could be of interest to produce new anticancer drugs and to bypass the resistance mechanisms against podophyllotoxin-derived drugs.

* These two authors contributed equally to this work.


Supporting Information

NMR data of the compounds and mass spectra analyses of extracts as well as the dose-response curves of the extracts are available as Supporting Information.

 
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