title: Oridonin inhibits BxPC-3 cell growth through cell apoptosis.
abstract: Oridonin, an ent-kaurene diterpenoid extracted from the traditional Chinese herb Rabdosia rubescens, has multiple biological and pharmaceutical functions and has been used clinically for many years. While the antitumor function of oridonin has been corroborated by numerous lines of evidence, its anticancer mechanism has not been well documented. In this study, the pancreatic cancer cell line BxPC-3 was used as a model to investigate a possible anticancer mechanism of oridonin through examining its effects on cell viability. The results showed that oridonin affected cell viability in a time- and dose-dependent manner. After exposure to different oridonin concentrations, growth rates and cell cycle arrest of BxPC-3 cells were significantly reduced compared with untreated cells, suggesting its effects on proliferation inhibition. Detailed signaling pathway analysis by western blot analysis revealed that low-dose oridonin treatment inhibited BxPC-3 cell proliferation by up-regulating p53 and down-regulating cyclin-dependent kinase 1 (CDK1), which led to cell cycle arrest in the G2/M phase. A high-dose oridonin not only arrested BxPC-3 cells in the G2/M phase but also induced cell accumulation in the S phase, presumably through γH2AX up-regulation and DNA damage. In addition, our results showed that a cell subpopulation was stained with propidium iodide after oridonin treatment. Protein quantification showed that cleaved poly(ADP-ribose) polymerase (PARP) expression was increased after a high-dose oridonin treatment, especially after long-term exposure. Accompanied by the increased level of deactivated PARP in BxPC-3 cells, the apoptosis initiators caspase-3 and caspase-7 expressions were also significantly increased, suggesting that caspase-mediated apoptosis contributed to cell death.
authors: Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China.
authors: Bin
authors: B
authors: Xu
authors: College of Medical Technology, Zhejiang Chinese Medical University, Hangzhou 310053, China.
authors: Wen
authors: W
authors: Shen
authors: School of Medicine, Jinggangshan University, Ji'an 343000, China.
authors: Xing
authors: X
authors: Liu
authors: College of Medical Technology, Zhejiang Chinese Medical University, Hangzhou 310053, China.
authors: Ting
authors: T
authors: Zhang
authors: College of Medical Technology, Zhejiang Chinese Medical University, Hangzhou 310053, China.
authors: Jun
authors: J
authors: Ren
authors: National Centre for Stem Cell Research, Eskitis Institute for Drug Discovery, Griffith University, QLD 4111, Australia.
authors: Yongjun
authors: Y
authors: Fan
authors: College of Medical Technology, Zhejiang Chinese Medical University, Hangzhou 310053, China xujian832002@163.com.
authors: Jian
authors: J
authors: Xu
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D016203:CDC2 Protein Kinase; D020169:Caspases / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D045786:Diterpenes, Kaurane / Q000494:pharmacology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D037602:Isodon; D008516:Medicine, Chinese Traditional; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D045786:Diterpenes, Kaurane; C468783:H2AX protein, human; D006657:Histones; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C011959:oridonin; D011065:Poly(ADP-ribose) Polymerases; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases; D020169:Caspases
keywords: BxPC-3 cells; apoptosis; oridonin; pancreatic cancer; proliferation