| Targeted constitutive activation of signal transducer and activator of transcription 3 in human hepatocellular carcinoma cells by cucurbitacin B. | |
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MedLine Citation:
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PMID: 18521604 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Meixia Zhang; Hongliang Zhang; Chunyan Sun; Xiaolei Shan; Xiaolin Yang; Jesse Li-Ling; Yihui Deng |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-06-03 |
Journal Detail:
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Title: Cancer chemotherapy and pharmacology Volume: 63 ISSN: 1432-0843 ISO Abbreviation: Cancer Chemother. Pharmacol. Publication Date: 2009 Mar |
Date Detail:
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Created Date: 2009-01-27 Completed Date: 2009-03-31 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7806519 Medline TA: Cancer Chemother Pharmacol Country: Germany |
Other Details:
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Languages: eng Pagination: 635-42 Citation Subset: IM |
Affiliation:
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Department of Clinical Pharmacology, China Medical University, Shenyang, China. zhangmeixia@mail.cmu.edu.cn |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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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