Document Detail


Targeted constitutive activation of signal transducer and activator of transcription 3 in human hepatocellular carcinoma cells by cucurbitacin B.
MedLine Citation:
PMID:  18521604     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: To determine the effect of cucurbitacin B on human hepatocellular carcinoma cell growth and apoptosis, and to explore the potential mechanisms. METHODS: In vitro viability of human hepatocellular carcinoma cell line (HepG2) was investigated using a 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. Morphologic changes of cells were evaluated through light microscopy. Cell cycle distribution was evaluated with flow cytometry following PI staining. Apoptosis was evaluated respectively with flow cytometry and fluorescent microscopy following Annexin V-FITC/PI and Hoechst 33258 staining. Western blot assays were performed to determine the expression of pSTAT3 and Bcl-2. Finally, in vivo effect of cucurbitacin B on the growth of HepG2 cells was determined in nude mice. RESULTS: The MTT assay showed that cucurbitacin B inhibited HepG2 cell viability in a dose and time-dependent manner. Cucurbitacin B treatment resulted in accumulation of cells at the S phase of cell cycle as well as apoptosis. Marked morphological changes, including condensation of chromatin, nuclear fragmentation and apoptotic bodies were clearly shown on Hoechst 33258 staining. Western blot showed that cucurbitacin B inhibited STAT3 phosphorylation and down-regulated the expression of Bcl-2. Growth of HepG2 tumor in nude mice was also inhibited by cucurbitacin B. CONCLUSION: Our results suggest that cucurbitacin B may have a therapeutic value in suppressing the growth of human hepatocellular carcinoma. The mechanism may be attributable to the suppression of STAT3 phosphorylation.
Authors:
Meixia Zhang; Hongliang Zhang; Chunyan Sun; Xiaolei Shan; Xiaolin Yang; Jesse Li-Ling; Yihui Deng
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-06-03
Journal Detail:
Title:  Cancer chemotherapy and pharmacology     Volume:  63     ISSN:  1432-0843     ISO Abbreviation:  Cancer Chemother. Pharmacol.     Publication Date:  2009 Mar 
Date Detail:
Created Date:  2009-01-27     Completed Date:  2009-03-31     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7806519     Medline TA:  Cancer Chemother Pharmacol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  635-42     Citation Subset:  IM    
Affiliation:
Department of Clinical Pharmacology, China Medical University, Shenyang, China. zhangmeixia@mail.cmu.edu.cn
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects*
Blotting, Western
Carcinoma, Hepatocellular / drug therapy*,  metabolism,  pathology
Cell Cycle / drug effects
Cell Proliferation / drug effects
Flow Cytometry
Humans
Liver Neoplasms, Experimental / drug therapy*,  metabolism,  pathology
Mice
Proto-Oncogene Proteins c-bcl-2 / metabolism
STAT3 Transcription Factor / metabolism*
Survival Rate
Triterpenes / pharmacology*
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
Chemical
Reg. No./Substance:
0/Proto-Oncogene Proteins c-bcl-2; 0/STAT3 Transcription Factor; 0/STAT3 protein, human; 0/Triterpenes; 6199-67-3/cucurbitacin B

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