title: Pseudolaric acid B induces mitotic catastrophe followed by apoptotic cell death in murine fibrosarcoma L929 cells.
abstract: Pseudolaric acid B (PAB) is the primary biologically active compound isolated from the root bark of P. kaempferi Gordon. Previous studies have demonstrated that PAB arrests cells in G2/M phase in several cancer cell lines without significantly perturbing the G2/M transition-associated proteins. CylinB1, a marker for mitotic phase arrest, was up-regulated in cells treated with PAB. Therefore, we investigated whether PAB affects cell cycle progression at the mitotic phase. The mitotic index increased during a 24h treatment with PAB, suggesting that PAB arrested cell cycle progression at mitosis. In addition, after a prolonged mitotic arrest, the cells underwent mitotic catastrophe. After an extended treatment with PAB (longer than 24h), the protein levels of cylinB1 and cdc2 significantly decreased in both nuclear and cytosolic extracts. According to these results, we concluded that mitotic slippage could be due to the inactivation of the cylinB1-cdc2 complex resulting from prolonged treatment with PAB. The cells undergoing mitotic catastrophe died via apoptosis.
authors.affiliation: China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Min
authors.initials: M
authors.lastname: Qi
authors.forename: Guodong
authors.initials: G
authors.lastname: Yao
authors.forename: Simiao
authors.initials: S
authors.lastname: Fan
authors.forename: Weiwei
authors.initials: W
authors.lastname: Cheng
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Tashiro
authors.forename: Satoshi
authors.initials: S
authors.lastname: Onodera
authors.forename: Takashi
authors.initials: T
authors.lastname: Ikejima
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D050256:Antimitotic Agents / Q000009:adverse effects / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D016203:CDC2 Protein Kinase / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D056744:Cyclin B1 / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D004224:Diterpenes / Q000009:adverse effects / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005354:Fibrosarcoma / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D015726:Giant Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051379:Mice; D008938:Mitosis / Q000187:drug effects*; D009363:Neoplasm Proteins / Q000378:metabolism; D014463:Ultrasonography
chemical_list: D050256:Antimitotic Agents; D000972:Antineoplastic Agents, Phytogenic; C534700:Ccnb1 protein, mouse; D056744:Cyclin B1; D004224:Diterpenes; D009363:Neoplasm Proteins; C058391:pseudolaric acid B; D016203:CDC2 Protein Kinase