title: Aspidin BB, a phloroglucinol derivative, induces cell cycle arrest and apoptosis in human ovarian HO-8910 cells.
abstract: Aspidin BB, an effective phloroglucinol derivative from Dryopteris fragrans (L.) Schott, has been previously reported to exert high biological activities. In this study, we analyzed the underlying mechanisms of aspidin BB on human ovarian cancer cell line, HO-8910. Aspidin BB significantly inhibited HO-8910 cell proliferation in a dose- and time-dependent manner. The IC50 values were 15.02, 25.79 and 68.81μM after 72, 48 and 24h treatment, respectively. Meanwhile, aspidin BB markedly induced apoptosis evidenced by characteristic apoptotic morphological changes, nuclear DNA fragmentation, annexin V-FITC/propidium iodide (PI) double staining and S peak. Western blot analysis showed that aspidin BB suppressed Bcl-2 expression and enhanced Bax expression to desintegrate the outer mitochondrial membrane, then caused cytochrome c release which led to the activation of effector caspase-3, and further cleaved the poly ADP-ribose polymerase (PARP) in the nucleus, finally induced cell apoptosis. Furthermore, aspidin BB provoked S phase arrest in HO-8910 cells with up-regulation of pRb, E2F1, CDK2, cyclin E and cyclin A proteins. Taken together, these findings support the conclusion that aspidin BB exhibits cytotoxicity towards human ovarian cancer HO-8910 cells through induction of apoptosis via mitochondrial pathway and arresting cell cycle progression in S phase.
authors.affiliation: State Engineering Laboratory of Bio-Resource Eco-Utilization, Northeast Forestry University, Harbin 150040, PR China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Sun
authors.forename: Fansong
authors.initials: F
authors.lastname: Mu
authors.forename: Chunying
authors.initials: C
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Meng
authors.initials: M
authors.lastname: Luo
authors.forename: Yujie
authors.initials: Y
authors.lastname: Fu
authors.forename: Yuangang
authors.initials: Y
authors.lastname: Zu
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004587:Electrophoresis, Agar Gel; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015394:Molecular Structure; D010051:Ovarian Neoplasms / Q000188:drug therapy; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D010696:Phloroglucinol; C010302:aspidin BB