title: Synergistic effect of cyclodextrins and methyl jasmonate on taxane production in Taxus x media cell cultures.
abstract: Methyl jasmonate and cyclodextrins are proven effective inducers of secondary metabolism in plant cell cultures. Cyclodextrins, which are cyclic oligosaccharides, can form inclusion complexes with nonhydrophilic secondary products, thus increasing their excretion from the producer cells to the culture medium. In the present work, using a selected Taxus x media cell line cultured in a two-stage system, the relationship between taxane production and the transcript profiles of several genes involved in taxol metabolism was studied to gain more insight into the mechanism by which these two elicitors regulate the biosynthesis and excretion of taxol and related taxanes. Gene expression was not clearly enhanced by the presence of cyclodextrins in the culture medium and variably induced by methyl jasmonate, but when the culture was supplemented with both elicitors, a synergistic effect on transcript accumulation was observed. The BAPT and DBTNBT genes, which encode the last two transferases involved in the taxol pathway, appeared to control limiting biosynthetic steps. In the cell cultures treated with both elicitors, the produced taxanes were found mainly in the culture medium, which limited retroinhibition processes and taxane toxicity for the producer cells. The expression level of a putative ABC gene was found to have increased, suggesting it played a role in the taxane excretion. Taxol biosynthesis was clearly increased by the joint action of methyl jasmonate and cyclodextrins, reaching production levels 55 times higher than in nonelicited cultures.
authors.affiliation: Department of Plant Biology, Faculty of Biology, University of Murcia, Campus de Espinardo, Murcia, Spain.
authors.forename: Ana-Belén
authors.initials: AB
authors.lastname: Sabater-Jara
authors.forename: Miriam
authors.initials: M
authors.lastname: Onrubia
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Moyano
authors.forename: Mercedes
authors.initials: M
authors.lastname: Bonfill
authors.forename: Javier
authors.initials: J
authors.lastname: Palazón
authors.forename: María A
authors.initials: MA
authors.lastname: Pedreño
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Cusidó
mesh_terms: D000085:Acetates / Q000494:pharmacology*; D053898:Biosynthetic Pathways; D001952:Bridged-Ring Compounds / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D003505:Cyclodextrins / Q000494:pharmacology*; D003517:Cyclopentanes / Q000494:pharmacology*; D004357:Drug Synergism; D018506:Gene Expression Regulation, Plant; D054883:Oxylipins / Q000494:pharmacology*; D010940:Plant Proteins / Q000235:genetics; D043823:Taxoids / Q000737:chemistry / Q000378:metabolism*; D020946:Taxus / Q000737:chemistry / Q000187:drug effects*
chemical_list: D000085:Acetates; D001952:Bridged-Ring Compounds; D003505:Cyclodextrins; D003517:Cyclopentanes; D054883:Oxylipins; D010940:Plant Proteins; D043823:Taxoids; C080625:taxane; C072239:methyl jasmonate
keywords: cell cultures; cyclodextrins; gene expression; methyl jasmonate; taxane production