title: Investigation of the Lignan Content in Extracts from Linum, Callitris and Juniperus Species in Relation to Their In Vitro Antiproliferative Activities.
abstract: Podophyllotoxin, a lignan still extracted from the rhizomes ofPodophyllum 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 ofP. 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 asLinum flavum, as well as someJuniperusandCallitrisspecies were investigated for their lignan content, and thein vitroantiproliferative 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 theirin vitroantiproliferative activity. The genusJuniperuswas the most promising given itsin vitroantiproliferative effects, which were also observed with extracts fromL. flavumandCallitrisspecies.Thein vitroantiproliferative 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.
authors: LBLGC, Université d'Orléans, Orléans, France.
authors: Joël
authors: J
authors: Doussot
authors: Faculté de Pharmacie, Laboratoire de Cancérologie et de Toxicologie Expérimentale, Université Libre de Bruxelles, Brussels, Belgium.
authors: Véronique
authors: V
authors: Mathieu
authors: Plate-forme HRMS Spectrométrie de Masse Haute Résolution, Fédération de Recherche Physique et Chimie du Vivant, Université d'Orléans, Orléans, France.
authors: Cyril
authors: C
authors: Colas
authors: Biologie des Plantes et Innovation, Université de Picardie Jules Verne, Amiens, France.
authors: Roland
authors: R
authors: Molinié
authors: LBLGC, Université d'Orléans, Orléans, France.
authors: Cyrielle
authors: C
authors: Corbin
authors: LBLGC, Université d'Orléans, Orléans, France.
authors: Josiane
authors: J
authors: Montguillon
authors: Faculté de Pharmacie, Laboratoire de Cancérologie et de Toxicologie Expérimentale, Université Libre de Bruxelles, Brussels, Belgium.
authors: Laeticia
authors: L
authors: Moreno Y Banuls
authors: LBLGC, Université d'Orléans, Orléans, France.
authors: Sullivan
authors: S
authors: Renouard
authors: LBLGC, Université d'Orléans, Orléans, France.
authors: Frédéric
authors: F
authors: Lamblin
authors: Centro de Investigacion y Asistencia en Tecnología y Diseno del Estado de Jalisco, Guadalajara, Mexico.
authors: Patricia
authors: P
authors: Dupré
authors: Institut de Chimie Organique et Analytique, Université d'Orléans, Orléans, France.
authors: Benoit
authors: B
authors: Maunit
authors: Faculté de Pharmacie, Laboratoire de Cancérologie et de Toxicologie Expérimentale, Université Libre de Bruxelles, Brussels, Belgium.
authors: Robert
authors: R
authors: Kiss
authors: LBLGC, Université d'Orléans, Orléans, France.
authors: Christophe
authors: C
authors: Hano
authors: LBLGC, Université d'Orléans, Orléans, France.
authors: Eric
authors: E
authors: Lainé
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D053898:Biosynthetic Pathways; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D029779:Cupressaceae / Q000737:chemistry*; D004357:Drug Synergism; D004365:Drugs, Chinese Herbal; D019597:Flax / Q000737:chemistry*; D006801:Humans; D018653:Juniperus / Q000737:chemistry*; D017705:Lignans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D011034:Podophyllotoxin / Q000031:analogs & derivatives / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology
chemical_list: C502514:6-methoxypodophyllotoxin; D000970:Antineoplastic Agents; D004365:Drugs, Chinese Herbal; D017705:Lignans; D010936:Plant Extracts; C014451:deoxypodophyllotoxin; D011034:Podophyllotoxin