title: Cucurbitacin E Induces G(2)/M Phase Arrest through STAT3/p53/p21 Signaling and Provokes Apoptosis via Fas/CD95 and Mitochondria-Dependent Pathways in Human Bladder Cancer T24 Cells.
abstract: Cucurbitacin E, a tetracyclic triterpenes compound extracted from cucurbitaceous plants, has been shown to exhibit anticancer and anti-inflammatory activities. The purpose of this study was to elucidate whether cucurbitacin E promotes cell cycle arrest and induces apoptosis in T24 cells and further to explore the underlying molecular mechanisms. The effects of cucurbitacin E on T24 cell's growth and accompanied morphological changes were examined by MTT assay and a phase-contrast microscope. DNA content, mitochondrial membrane potential (ΔΨ(m)) and annexin V/PI staining were determined by flow cytometry. The protein levels were measured by Western blotting. Our results demonstrated that cucurbitacin E-induced G(2)/M arrest was associated with a marked increase in the levels of p53, p21 and a decrease in phospho-signal transducer and activator of transcription 3 (STAT3), cyclin-dependent kinase 1 (CDK1) and cyclin B. Cucurbitacin E-triggered apoptosis was accompanied with up-regulation of Fas/CD95, truncated BID (t-BID) and a loss of ΔΨ(m), resulting in the releases of cytochrome c, apoptotic protease activating factor 1 (Apaf-1) and apoptosis-inducing factor (AIF), and sequential activation of caspase-8, caspase-9, and caspase-3. Our findings provided the first evidence that STAT3/p53/p21 signaling, Fas/CD95 and mitochondria-dependent pathways play critical roles in cucurbitacin E-induced G(2)/M phase arrest and apoptosis of T24 cells.
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung 404, Taiwan.
authors.forename: Wen-Wen
authors.initials: WW
authors.lastname: Huang
authors.forename: Jai-Sing
authors.initials: JS
authors.lastname: Yang
authors.forename: Meng-Wei
authors.initials: MW
authors.lastname: Lin
authors.forename: Po-Yuan
authors.initials: PY
authors.lastname: Chen
authors.forename: Shang-Ming
authors.initials: SM
authors.lastname: Chiou
authors.forename: Fu-Shin
authors.initials: FS
authors.lastname: Chueh
authors.forename: Yu-Hsuan
authors.initials: YH
authors.lastname: Lan
authors.forename: Shu-Jen
authors.initials: SJ
authors.lastname: Pai
authors.forename: Minoru
authors.initials: M
authors.lastname: Tsuzuki
authors.forename: Wai-Jane
authors.initials: WJ
authors.lastname: Ho
authors.forename: Jing-Gung
authors.initials: JG
authors.lastname: Chung