title: Ellagic acid and embelin affect key cellular components of pancreatic adenocarcinoma, cancer, and stellate cells.
abstract: Ellagic acid is a polyphenolic phytochemical present in many fruits and nuts with anticancer properties demonstrated in experimental tumor studies. Embelin is a benzoquinone phytochemical isolated from the Japanese herb Ardisiae Japonicae and has been shown to induce apoptosis in cancer cells. We found that ellagic acid and embelin each dose-dependently increased apoptosis and inhibited proliferation in human pancreatic cancer cells, MIA PaCa-2 and HPAF-II cells, and in pancreatic stellate cells, which are progenitors of pancreatic cancer desmoplasia. In each of these cell types, combinations of ellagic acid and embelin at low micromolar concentrations (0.5-3 μM) induced synergistic increases in apoptosis and decreases in proliferation. Ellagic acid decreased NF-κB transcriptional activity, whereas embelin decreased STAT-3 phosphorylation and protein expression of its downstream target survivin in cancer cells. In vivo dietary ellagic acid alone or in combination with embelin decreased tumor size and tumor cellularity in a subcutaneous xenograft mouse model of pancreatic cancer. These results show that ellagic acid and embelin interact with divergent intracellular signaling pathways resulting in augmentation of apoptosis and inhibition of proliferation at low micromolar concentrations for the key cellular components of pancreatic adenocarcinoma.
authors.affiliation: a Veterans Affairs Greater Los Angeles Healthcare System , Los Angeles , California , USA.
authors.forename: Mouad
authors.initials: M
authors.lastname: Edderkaoui
authors.forename: Aurelia
authors.initials: A
authors.lastname: Lugea
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Hui
authors.forename: Guido
authors.initials: G
authors.lastname: Eibl
authors.forename: Qing-Yi
authors.initials: QY
authors.lastname: Lu
authors.forename: Aune
authors.initials: A
authors.lastname: Moro
authors.forename: Xuyang
authors.initials: X
authors.lastname: Lu
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.forename: Vay-Liang
authors.initials: VL
authors.lastname: Go
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Pandol
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D016227:Benzoquinones / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004610:Ellagic Acid / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D058954:Pancreatic Stellate Cells / Q000187:drug effects*; D010766:Phosphorylation; D064209:Phytochemicals / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D016227:Benzoquinones; D016328:NF-kappa B; D064209:Phytochemicals; D010936:Plant Extracts; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D004610:Ellagic Acid; C010945:embelin