title: The sesquiterpene lactone polymatin B from Smallanthus sonchifolius induces different cell death mechanisms in three cancer cell lines.
abstract: A 8β-angeloyloxy-9α-hydroxy-14-oxo-acanthospermolide and five known melampolide sesquiterpene lactones (uvedalin, enhydrin, polymatin B, sonchifolin, and fluctuanin) were isolated from the leaves of Smallanthus sonchifolius. The compounds were identified by 1D-, 2D-NMR, HRMS, IR and UV analyses. In vitro cytotoxicity assays (MTT) showed that these sesquiterpene lactones display poor cytotoxic effects on peripheral blood mononuclear cells (PBMC) of healthy human subjects, whereas a strong cytotoxicity was observed in leukemia and pancreas cancer cells. For the mechanism of action of polymatin B, oxidative stress seems to be involved. Interestingly, reactive oxygen species (ROS) formation mainly induced different effects: apoptosis in CCRF-CEM cells, necroptosis in CEM-ADR5000 cells through induction of RIP1K, neither apoptosis nor necroptosis in MIA-PaCa-2 cells. Additionally, cells also died partly by necrosis.
authors.affiliation: Department of Pharmaceutical Biology and Biotechnology, Faculty of Chemistry and Pharmacy, University of Freiburg, Stefan-Meier-Str. 19 (VF), D-79104 Freiburg, Germany; Spemann Graduate School of Biology and Medicine (SGBM), Albert Ludwigs University Freiburg, Albertstrasse 19a, D-79104 Freiburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: De Ford
authors.affiliation: Cátedra de Farmacognosia, IQUIMEFA (UBA-CONICET), Facultad de Farmacia y Bioquímica, UBA, Junín 956, Buenos Aires 1113, Argentina.
authors.forename: Jerónimo L
authors.initials: JL
authors.lastname: Ulloa
authors.affiliation: INQUINOA (CONICET), Facultad de Bioquímica, Química y Farmacia, UNT, Ayacucho 971 (T4000INI), San Miguel de Tucumán, Argentina.
authors.forename: César A N
authors.initials: CAN
authors.lastname: Catalán
authors.affiliation: Facultad de Ciencias Naturales, Instituto de Ecología Regional (IER), Universidad Nacional de Tucumán, C. C. 34, 4107 Yerba Buena, Tucumán, Argentina.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Grau
authors.affiliation: Cátedra de Farmacognosia, IQUIMEFA (UBA-CONICET), Facultad de Farmacia y Bioquímica, UBA, Junín 956, Buenos Aires 1113, Argentina.
authors.forename: Virginia S
authors.initials: VS
authors.lastname: Martino
authors.affiliation: Cátedra de Farmacognosia, IQUIMEFA (UBA-CONICET), Facultad de Farmacia y Bioquímica, UBA, Junín 956, Buenos Aires 1113, Argentina. Electronic address: lmusch@ffyb.uba.ar.
authors.forename: Liliana V
authors.initials: LV
authors.lastname: Muschietti
authors.affiliation: Department of Pharmaceutical Biology and Biotechnology, Faculty of Chemistry and Pharmacy, University of Freiburg, Stefan-Meier-Str. 19 (VF), D-79104 Freiburg, Germany; Spemann Graduate School of Biology and Medicine (SGBM), Albert Ludwigs University Freiburg, Albertstrasse 19a, D-79104 Freiburg, Germany.
authors.forename: Irmgard
authors.initials: I
authors.lastname: Merfort
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D019659:Asteraceae / Q000737:chemistry*; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D006801:Humans; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology*; D015458:Leukemia, T-Cell / Q000188:drug therapy / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D018384:Oxidative Stress / Q000187:drug effects; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology*; D045788:Sesquiterpenes, Germacrane / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D007783:Lactones; D012717:Sesquiterpenes; D045788:Sesquiterpenes, Germacrane; C521984:enhydrin; C000605835:polymatin B; C000605836:uvedalin
keywords: Asteraceae; Cytotoxicity; Sesquiterpene lactones; Smallanthus sonchifolius