title: Multiple anticancer effects of damsin and coronopilin isolated from Ambrosia arborescens on cell cultures.
abstract: Terpenoids in plants are important sources for drug discovery. In this study, we extracted damsin and coronopilin, two sesquiterpene lactones, from Ambrosia arborescens and examined their anticancer effects on cell cultures. Damsin and coronopilin inhibited cell proliferation, DNA biosynthesis and formation of cytoplasmic DNA histone complexes in Caco-2 cells, with damsin being more potent than coronopilin. Further studies using the luciferase reporter system showed that damsin and coronopilin also inhibited expressions of nuclear factor-κB (NF-κB) and signal transducer and activator of transcription-3 (STAT3), indicating that these sesquiterpenes can interfere with NF-κB and STAT3 pathways. Finally, we examined the effects of two synthetic dibrominated derivatives of damsin, 11α,13-dibromodamsin and 11β,13-dibromodamsin. While bromination appeared to weaken the antiproliferative effects of damsin, the β epimer had strong inhibitory effects on STAT3 activation. In conclusion, the sesquiterpene lactones damsin and coronopilin have inhibitory effects on cell proliferation, DNA biosynthesis and NF-κB and STAT3 pathways, thus being potentially important for discovery of drugs against cancer.
authors.affiliation: Biomedical Center B11, Gastroenterology and Nutrition Lab, Institution of Clinical Sciences, Lund University, S-221 84 Lund, Sweden. Rui-dong.duan@med.lu.se.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Villagomez
authors.forename: Gloria C
authors.initials: GC
authors.lastname: Rodrigo
authors.forename: Isidro G
authors.initials: IG
authors.lastname: Collado
authors.forename: Marco A
authors.initials: MA
authors.lastname: Calzado
authors.forename: Eduardo
authors.initials: E
authors.lastname: Muñoz
authors.forename: Björn
authors.initials: B
authors.lastname: Åkesson
authors.forename: Olov
authors.initials: O
authors.lastname: Sterner
authors.forename: Giovanna R
authors.initials: GR
authors.lastname: Almanza
authors.forename: Rui-Dong
authors.initials: RD
authors.lastname: Duan
mesh_terms: D031164:Ambrosia / Q000737:chemistry*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D052176:Azulenes / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004261:DNA Replication / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007783:Lactones / Q000302:isolation & purification / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D009369:Neoplasms / Q000473:pathology; D050796:STAT3 Transcription Factor / Q000378:metabolism; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D052176:Azulenes; D007783:Lactones; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D012717:Sesquiterpenes; C584613:coronopilin; C012266:damsin
keywords: Ambrosia arborescens; NF-κB; STAT3; apoptosis; cell proliferation; chemoselective bromination; coronopilin; damsin; sesquiterpenes