title: Ferrearin C induces apoptosis via heme oxygenase-1 (HO-1) induction in neuroblastoma.
abstract: We investigated the cytotoxicity of six neolignans (1-6), which are similar in structure to furanocyclohexenone with an angular allyl group, in human neuroblastoma cell lines (IMR-32, LA-N-1, NB-39, SK-N-SH) and normal cells [human umbilical vein endothelial cells (HUVEC) and human dermal fibroblasts (HDF)] using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Two neolignans, ferrearin C (1) and 2, showed significant cytotoxicity in neuroblastoma cells. Typical morphologic features of apoptosis were observed for the ferrearin-type neolignans using Hoechst 33342, and apoptotic cytoplasmic membrane inversion was also induced by ferrearin-type neolignans in IMR-32. Furthermore, a Proteome Profiler Array showed that the ferrearin-type neolignans induced the marked expression of heme oxygenase-1 (HO-1). In a western blot analysis, ferrearin C (1) increased the level of Bax and reduced the level of survivin, indicating the activation of the mitochondrial pathway of apoptosis.
authors.affiliation: School of Pharmacy, Nihon University, Funabashi, Chiba, 274-8555, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Hayama
authors.forename: Keiichi
authors.initials: K
authors.lastname: Tabata
authors.forename: Taketo
authors.initials: T
authors.lastname: Uchiyama
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Fujimoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D017705:Lignans / Q000737:chemistry / Q000494:pharmacology*; D008954:Models, Biological; D015394:Molecular Structure; D009447:Neuroblastoma / Q000378:metabolism*; D000077022:Survivin; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D017705:Lignans; D000077022:Survivin; D051028:bcl-2-Associated X Protein; D051547:Heme Oxygenase-1