Investigation of the lignan content in extracts from linum, callitris and juniperus species in relation to their In vitro antiproliferative activities
2017
Doussot, Joel | Mathieu, Veronique | Colas, Cyril | Molinie, Roland | Corbin, Cyrielle | Montguillon, Josiane | Banuls, Laeticia Moreno Y. | Renouard, Sullivan | Lamblin, Frédéric | Dupre, Patricia | Maunit, Benoit | Kiss, Robert | Hano, Christophe | Laine, Eric | Conservatoire National des Arts et Métiers [Cnam] (Cnam) | Laboratoire de Biologie des Ligneux et des Grandes Cultures (LBLGC) ; Institut National de la Recherche Agronomique (INRA)-Université d'Orléans (UO) | Faculté de Pharmacie, Laboratoire de Cancérologie et de Toxicologie Expérimentale ; Université libre de Bruxelles (ULB) | Biologie des Plantes et Innovation - UR UPJV 3900 (BIOPI) ; Université de Picardie Jules Verne (UPJV) | Ctr Invest & Asistencia Tecnol & Diseno Estado Ja | Institut de Chimie Organique et Analytique (ICOA) ; Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS) | Conseil General de l'Eure et Loir" (France); "La Ligue Contre le Cancer d'Eure et Loir" (France); Belgian Brain Tumor Support (Belgium)
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 LCHRMS 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.
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