title: ATM-p53 pathway causes G2/M arrest, but represses apoptosis in pseudolaric acid B-treated HeLa cells.
abstract: Pseudolaric acid B (PAB) is a diterpene acid, isolated from the root and trunk bark of Pseudolarix kaempferi Gordon (Pinaceae). Previous studies demonstrated that PAB induced G2/M arrest and apoptosis in several cancer cell lines, but the relationship between G2/M arrest and apoptosis is still unclear. We examined the relevant signaling pathways for human cervical carcinoma HeLa cells treated with 1 μM PAB. Intriguingly, we found that activation of ATM-p53 signaling pathway by the treatment with 1 μM PAB played a protective role for the subsequent apoptosis. Although the treatment with 1 μM PAB up-regulated the expression of cyclin B1 and p-Histone 3 (mitotic markers) at 12 h, the expression decreased at 24 and 36 h along with the up-down expression of mitotic markers. The expressions of p-ATM and p-p53 that were involved in G2/M arrest increased at 12h after treatment with PAB. However, a prolonged treatment with PAB (longer than 24 h) caused cell apoptosis. When the cells were arrested in G1 or S phase by the treatment with serum starvation, cytosine β-D-arabinofuranoside (Ara-C) or hydroxyurea (Hu), the apoptotic ratio induced by PAB decreased.
authors.affiliation: China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Guodong
authors.initials: G
authors.lastname: Yao
authors.affiliation: China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016, China; Tianjin Taiyang Pharmaceutical Co., Ltd., Tianjin 300457, China.
authors.forename: Min
authors.initials: M
authors.lastname: Qi
authors.affiliation: China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Ji
authors.affiliation: China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016, China; Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
authors.forename: Simiao
authors.initials: S
authors.lastname: Fan
authors.affiliation: China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Xu
authors.affiliation: China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Institute for Clinical and Biomedical Sciences, Kyoto 603-8072, Japan.
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Tashiro
authors.affiliation: Department of Clinical and Biomedical Sciences, Showa Pharmaceutical University, Tokyo 194-8543, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Onodera
authors.affiliation: China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: ikejimat@vip.sina.com.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ikejima
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D004224:Diterpenes; D016159:Tumor Suppressor Protein p53; C058391:pseudolaric acid B; D064007:Ataxia Telangiectasia Mutated Proteins
keywords: ATM; Apoptosis; G2/M arrest; Pseudolaric acid B; p53