title: The eudesmanolide tanapsin from Tanacetum oshanahanii and its acetate induce cell death in human tumor cells through a mechanism dependent on reactive oxygen species.
abstract: In this study the cytotoxicities of two species of Tanacetum were evaluated against human tumor cells. Tanacetum oshanahanii extract was more cytotoxic than Tanacetum ptarmiciflorum. Analyses of both extracts of Tanacetum by ultrahigh performance liquid chromatography-tandem mass spectrometry revealed that T. oshanahanii extract contains the eudesmanolide tanapsin, while T. ptarmiciflorum lacks this sesquiterpene lactone. Tanapsin was cytotoxic against leukemia and melanoma cells, including cells that overexpress Bcl-2 and Bcl-xL, with IC50 values of approximately 10 µM, but not against quiescent or proliferating human peripheral blood mononuclear cells. Treatment of cells with tanapsin induced apoptosis. This was prevented by the non-specific caspase inhibitor z-VAD-fmk, and reduced by the selective caspase-3/7 inhibitor z-DEVD-fmk. Tanapsin acetate was also cytotoxic against leukemia and melanoma cells and a potent apoptotic inducer. Tanapsin-induced cell death was found to be associated with (i) the loss of inner mitochondrial membrane potential (ΔΨm) and release of mitochondrial cytochrome c, (ii) the activation of multiple caspases and the mitogen-activated protein kinase pathway, and (iii) an increase in reactive oxygen species generation. Generation of reactive oxygen species in response to tanapsin seems to play a crucial role in the cell death process since the antioxidant N-acetyl-l-cysteine blocked both ROS generation and cell death.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Las Palmas de Gran Canaria, Plaza Dr. Pasteur s/n, 35016 Las Palmas de Gran Canaria, Spain.
authors.forename: Gledy
authors.initials: G
authors.lastname: Negrín
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Las Palmas de Gran Canaria, Plaza Dr. Pasteur s/n, 35016 Las Palmas de Gran Canaria, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Rubio
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Las Palmas de Gran Canaria, Plaza Dr. Pasteur s/n, 35016 Las Palmas de Gran Canaria, Spain.
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Marrero
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Las Palmas de Gran Canaria, Plaza Dr. Pasteur s/n, 35016 Las Palmas de Gran Canaria, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Quintana
authors.affiliation: Department of Chemistry, University of Las Palmas de Gran Canaria, Campus de Tafira, 35017 Las Palmas de Gran Canaria, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Eiroa
authors.affiliation: Department of Chemistry, University of Las Palmas de Gran Canaria, Campus de Tafira, 35017 Las Palmas de Gran Canaria, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Triana
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Las Palmas de Gran Canaria, Plaza Dr. Pasteur s/n, 35016 Las Palmas de Gran Canaria, Spain. Electronic address: festevez@dbbf.ulpgc.es.
authors.forename: Francisco
authors.initials: F
authors.lastname: Estévez
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D015394:Molecular Structure; D035261:Plant Components, Aerial / Q000737:chemistry; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012717:Sesquiterpenes / Q000494:pharmacology*; D045787:Sesquiterpenes, Eudesmane / Q000494:pharmacology*; D031203:Tanacetum / Q000737:chemistry*; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C000595707:BCL2 protein, human; C494811:BCL2L1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D012717:Sesquiterpenes; D045787:Sesquiterpenes, Eudesmane; D051020:bcl-X Protein; C476916:eudesmanolide; C000601534:tanapsin
keywords: Apoptosis; Caspases; Cytotoxic activity; DNA fragmentation; Eudesmanolides; Poly(ADP-ribose) polymerase