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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.
MedLine Citation:
PMID:  22272214     Owner:  NLM     Status:  In-Data-Review    
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.
Wen-Wen Huang; Jai-Sing Yang; Meng-Wei Lin; Po-Yuan Chen; Shang-Ming Chiou; Fu-Shin Chueh; Yu-Hsuan Lan; Shu-Jen Pai; Minoru Tsuzuki; Wai-Jane Ho; Jing-Gung Chung
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Publication Detail:
Type:  Journal Article     Date:  2012-01-09
Journal Detail:
Title:  Evidence-based complementary and alternative medicine : eCAM     Volume:  2012     ISSN:  1741-4288     ISO Abbreviation:  Evid Based Complement Alternat Med     Publication Date:  2012  
Date Detail:
Created Date:  2012-01-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101215021     Medline TA:  Evid Based Complement Alternat Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  952762     Citation Subset:  -    
Department of Biological Science and Technology, China Medical University, Taichung 404, Taiwan.
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