title: Oridonin nanosuspension was more effective than free oridonin on G2/M cell cycle arrest and apoptosis in the human pancreatic cancer PANC-1 cell line.
abstract: Oridonin, a diterpenoid isolated from Rabdosia rubescencs, has been reported to have antitumor effects. However, low solubility has limited its clinical applications. Preparation of drugs in the form of nanosuspensions is an extensively utilized protocol. In this study, we investigated the anticancer activity of oridonin and oridonin nanosuspension on human pancreatic carcinoma PANC-1 cells. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to investigate the effect of oridonin on cell growth. Propidium iodide and Hoechst 33342 staining were used to detect morphologic changes. The percentage of apoptosis and cell cycle progression was determined by flow cytometric method staining with propidium iodide. Annexin V-fluorescein isothiocyanate (FITC)/PI staining was used to evaluate cell apoptosis by flow cytometry. Caspase-3 activity was measured by spectrophotometry. The apoptotic and cell cycle protein expression were determined by Western blot analysis. Both oridonin and oridonin nanosuspension induced apoptosis and G(2)/M phase cell cycle arrest, and the latter had a more significant cytotoxic effect. The ratio of Bcl-2/Bax protein expression was decreased and caspase- 3 activity was stimulated. The expression of cyclin B1 and p-cdc2 (T161) was suppressed. Our results showed that oridonin nanosuspension was more effective than free oridonin on G(2)/M cell cycle arrest and apoptosis in the human pancreatic cancer PANC-1 cell line.
authors.affiliation: Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan, People’s Republic of China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Qi
authors.forename: Dianrui
authors.initials: D
authors.lastname: Zhang
authors.forename: Xia
authors.initials: X
authors.lastname: Xu
authors.forename: Feifei
authors.initials: F
authors.lastname: Feng
authors.forename: Guijie
authors.initials: G
authors.lastname: Ren
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Chu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.forename: Keli
authors.initials: K
authors.lastname: Tian
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D045786:Diterpenes, Kaurane / Q000008:administration & dosage*; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D050997:Nanomedicine; D049329:Nanostructures / Q000008:administration & dosage; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013535:Suspensions; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C494826:BAX protein, human; D018797:Cell Cycle Proteins; D045786:Diterpenes, Kaurane; D019253:Proto-Oncogene Proteins c-bcl-2; D013535:Suspensions; D051028:bcl-2-Associated X Protein; C011959:oridonin; C505407:CASP3 protein, human; D053148:Caspase 3