title: Induction of G(2)/M phase arrest and apoptosis by oridonin in human laryngeal carcinoma cells.
abstract: Oridonin (1), an active component isolated from the plant Rabdosia rubescens, has been reported to exhibit antitumor effects. In this study, the mechanism involved in 1-induced growth inhibition, including apoptosis and G(2)/M phase arrest, in human laryngeal carcinoma HEp-2 cells deficient in functional p53, was investigated for the first time. Compound 1 triggered the mitochondrial apoptotic pathway, as indicated by increased Bax/Bcl-2 ratios, reduction of mitochondrial membrane potential (DeltaPsi(m)), and substantial increase in apoptosis-inducing factor (AIF) and cytochrome c. Inhibition of caspase-9 in HEp-2 cells did not protect the cells from 1-induced apoptosis, and cleaved caspase-9 was not detected, indicating that apoptosis occurred via a caspase-9-independent pathway. The results also suggested that G(2)/M phase arrest and apoptosis mediated by 1 occurred via a p53-independent but in a p21/WAF1-dependent manner in HEp-2 cells. In addition, the generation of reactive oxygen species (ROS) was found to be a critical mediator in growth inhibition induced by 1. Taken together, the results indicate that oridonin (1) is a potentially effective agent for the treatment of laryngeal squamous cell carcinoma.
authors.affiliation: China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, People's Republic of China.
authors.forename: Ning
authors.initials: N
authors.lastname: Kang
authors.forename: Jing-Hai
authors.initials: JH
authors.lastname: Zhang
authors.forename: Feng
authors.initials: F
authors.lastname: Qiu
authors.forename: Sheng
authors.initials: S
authors.lastname: Chen
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: D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell; D061945:Caspase Inhibitors; D002453:Cell Cycle / Q000187:drug effects*; D045786:Diterpenes, Kaurane / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D037602:Isodon / Q000737:chemistry; D007822:Laryngeal Neoplasms / Q000188:drug therapy*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D015394:Molecular Structure; D017382:Reactive Oxygen Species / Q000032:analysis
chemical_list: D061945:Caspase Inhibitors; D045786:Diterpenes, Kaurane; D017382:Reactive Oxygen Species; C011959:oridonin